volume 3 number 01 - Prevention and Research

Transcript

International Open Access Journal of Prevention and Research in Medicine
Director Prof. Francesco Tomei
VOLUME 3 NUMBER 01
JAN-MAR 2013
www.preventionandresearch.com
Jan-Mar 2013|P&R Scientific|Volume 3|N°1
IN THIS NUMBER
Antonelli MM, Antonelli W
pag. 01-06
Comparison of two systemic antibiotics for the prevention of complications in elective
colorectal surgery
Confronto di due antibiotici nella profilassi sistemica per la prevenzione di complicazioni nella
chirurgia elettiva colo-rettale
Capoano R, Tesori MC, Forcione AR, Lacroce G, Police A, Llange K, Donello C,
Gianfrancesco E, Lombardo F, Monacelli G, Salvati B
pag. 07-15
Limb-salvage surgery in trauma leg injuries. Does it offer patients better quality of life and
functional capacity than amputation?
La chirurgia di salvataggio d’arto dopo trauma degli arti può offrire ai pazienti una miglior qualità
vita e capacità funzionale rispetto all’amputazione?
Suppa M, Mecella M, Migliozzi E, Cossu F, Bertazzoni G, Catarci T
pag. 16-25
Testmed. Process management in Emergency Medicine.
Tesmed. Gestione dei processi nella medicina d’urgenza
De Angelis C, Compare R
pag. 26-33
Pathophysiology of acute postoperative pain and scientific rationale of "pre-emptive analgesia”
Fisiopatologia del dolore acuto post-operatorio e razionale scientifico della “pre-emptive
analgesia”
Paolucci V , Liberatori R, Pescaglini M, Sartorelli P
pag. 34-38
In vitro percutaneous penetration of polycyclic aromatic hydrocarbons from sunscreen creams
Penetrazione percutanea in vitro di idrocarburi policiclici aromatici dalle creme solari
Mandolesi S, De Sio S, Di Pastena C, Scala B, Loreti B, Corbosiero P, Sinibaldi F,
Sacco C, Mascia I, Cappelli L, Casale T, Mandolesi D
pag. 39-44
Chronic cerebro spinal venous insufficiency (CCSVI):a new hypothesis for Multiple Sclerosis
L’insufficienza venosa cronica cerebro spinale (CCSVI): una nuova ipotesi per la Sclerosi Multipla
pag. 45-49
Pontone S, Leonetti G, Brighi M, Pontone P
Enterobius vermicularis: endoscopic opportunistic diagnosis in a poorly symptomatic infection
Enterobius Vermicularis: una diagnosi endoscopica occasionale in una ossiuriasi paucisintomatica
pag. 50-59
Stefanati A, De Paris P, Nardini M, Boschetto P
Incidence of biological fluid-related accidents among interns of a University-Hospital
Studio di incidenza sugli infortuni a rischio biologico nel personale medico in formazione
specialistica in una azienda ospedaliero-universitaria
Comparison of two systemic antibiotics for the prevention
of complications in elective colorectal surgery
COMPARISON OF TWO SYSTEMIC ANTIBIOTICS FOR THE
PREVENTION OF COMPLICATIONS IN ELECTIVE COLORECTAL
SURGERY
CONFRONTO DI DUE ANTIBIOTICI NELLA PROFILASSI SISTEMICA PER LA
PREVENZIONE DI COMPLICAZIONI NELLA CHIRURGIA ELETTIVA COLO-RETTALE
Antonelli MM1, Antonelli W2
1
Pharmaceutical Service, Hospital of Macerata, Italy
2
Division of Surgery, Hospital of Macerata, Italy
1
Servizio Farmaceutico, Ospedale di Macerata
2
Divisione di Chirurgia, Ospedale di Macerata
Citation: Antonelli MM, Antonelli W. Comparison of two systemic antibiotics for the prevention of complications in elective
colorectal surgery. Prevent Res 2013; 3 (1): 01-06. Available from: http://www.preventionandresearch.com/ .
Key words: antibiotic systemic prophylaxis, elective colorectal surgery
Parole chiave: profilassi antibiotica sistemica, chirurgia colorettale elettiva
Abstract
The surgical site infections are the third more frequent hospital-acquired infection and 3/4 of the deaths occurred in
patients with surgical site infections are to relate to them. Antibiotic prophylax is crucial in the prevention of surgical
site infections, in particular types of surgical operations such as the colon an organ with high bacterial load. The use of
antibiotics, to be effective, it needs to be indicated for the type of surgical operation, pharmaceutical form, dose,
timing of administration appropriate to spectrum of activity targeted to bacteria most frequently encountered. The
inappropriate use of antibiotics in the prophylaxis of surgical site infection leads to the ineffectiveness of the
administration with an increased incidence of infections and the cost because it increases the days of hospitalization
and working days lost to sickness. It also increases the appearance iatrogenesis, the side effects of the drugs
administered. The inappropriate use of antibiotics in the prophylaxis besides increments the selection of resistant
strains. In a prospective randomized trial on 77 patients undergoing elective colorectal surgery, cefoxitin and
cephalothin were given as systemic antibiotic prophylaxis. Cefoxitin is a betalactamase stable cephalosporin-
1
cephamycin, especially effective against gram-negative organisms and Bacteroides species which are likely to be
present in postoperative infections after large bowel surgery. These organisms were frequently shown to be resistant
to the antibiotics used in systemic prophylaxis as cephalothin or ampicillin. All patients received low residue diet and
preoperative standard bowel preparation with saline enema and oral laxatives for 3 days before surgery excluding the
patients undergoing colo-sigmoidostomy closure operations. Two groups of 40 and 37 randomized patients were
studied. Cefoxitin group: the 40 patients received cefoxitin (2 gm) intravenously 30 minutes preoperatively, an
additional dose of 2 gm during surgery (over two hours) and then 2 gm 8h postpoperatively for 48 hours. Cephalothin
group: the 37 patients received cephalothin (2 gm) intravenously 2 hours preoperatively, 2 gm during surgery, and 2
gm every 6 hours postoperatively for 2 days. Postoperative sepsis occurred in 2/40 (5 %) of those given cefoxitin
compared to 9/37 (24.3 %) of those given cephalothin. The reduction in the infection rate in the group treated by
cefoxitin was statistically significant (p<0.02). Specific drug toxicity was not evidenced except for transient skin rashes
in two patients of both groups. In the patients with infectious complications aerobic and anaerobic bacteria were
present in most cases. B. fragilis, C. perfringens, E. coli, S. epidermidis, K. Penumoniae, Bacterioides, Peptococcus,
Corynebactrium, P. morganii, C. perfringens and B. melaninogenicus.
Abstract
Le infezioni del sito chirurgico rappresentano la terza infezione ospedaliera per frequenza e che circa i 3/4 dei decessi
occorsi in pazienti con infezioni del sito chirurgico sono da correlarsi alle stesse. Il ricorso alla profilassi antibiotica ha un
ruolo determinante nella prevenzione delle infezioni del sito chirurgico, particolarmente per alcuni tipi di interventi come
quelli del colon, dove è presente una alta carica batterica. L’utilizzo di antibiotici, perché sia efficace, occorre che sia
indicato per il tipo di intervento, con forma farmaceutica, dosi e tempi di somministrazione adeguati e spettro d'azione
mirato ai germi più frequentemente riscontrati. L’inappropriatezza dell'uso degli antibiotici nella profilassi dell’infezione
del sito chirurgico comporta l’inefficacia della somministrazione con aumentata incidenza di infezioni e relativo
incremento dei costi conseguenti all’aumento di giornate di degenza ed alle giornate lavorative perse per malattia, oltre
che la iatrogenesi correlata agli effetti indesiderati dei farmaci somministrati. L’uso non appropriato degli antibiotici
comporta in ambiente nosocomiale la selezione di ceppi resistenti che rende più difficoltoso l’approccio terapeutico alle
infezioni batteriche. In uno studio longitudinale randomizzato condotto su 77 pazienti sottoposti a chirurgia elettiva colorettale sono state somministrate cefossitina o cefalotina come profilassi antibiotica sistemica. Cefoxitina è una
cefalosporina resistente alle betalattamasi, particolarmente efficace contro i batteri gram-negativi e le specie
Bacteroides che possono essere presenti in caso di infezioni post-operatorie dopo l'intervento del grosso intestino. Questi
organismi mostrano spesso di essere resistenti agli antibiotici utilizzati nella profilassi sistemica come cefalotina o
ampicillina. Tutti i pazienti hanno ricevuto una dieta a basso residuo e una preparazione intestinale preoperatoria
standard con clistere salino e lassativi per via orale per 3 giorni prima dell'intervento chirurgico esclusi i pazienti
sottoposti a operazione di chiusura colo-sigmostomia. Due gruppi di 40 e 37 pazienti randomizzati sono stati studiati. Il
gruppo trattato con Cefoxitina: 40 pazienti hanno ricevuto cefoxitina (2 grammi) per via endovenosa 30 minuti prima
dell'intervento, una dose supplementare di 2 grammi durante l'intervento chirurgico (oltre due ore) e poi 2 gr 8h dopo
l'intervento per 48 ore. Il gruppo trattato con Cefalotina: dei 37 pazienti hanno ricevuto cefalotina (2 grammi) per via
endovenosa due ore prima dell'intervento, 2 gr durante l'intervento chirurgico, e 2 gr ogni 6 ore dopo l'intervento per 2
giorni. Le complicanze settiche si sono riscontrate in 2/40 (5%) del gruppo trattato con cefossitina, contro 9/37 (24.3%)
del gruppo trattato con cefalotina. La riduzione delle complicanze settiche post-operatorie nel gruppo trattato con
cefossitina è risultata statisticamente significativa (p<0.02). Non si sono riscontrati effetti collaterali di rilievo, fatta
eccezione per transitori rashes cutanei in due pazienti di entrambi i gruppi. Nei pazienti con complicanze infettive da
batteri aerobici ed anaerobici abbiamo isolato le seguenti specie B. fragilis, C. perfringens, E. coli, S. epidermidis, K.
Penumoniae, Bacterioides, Peptococcus, Corynebactrium, P. morganii, C. perfringens and B. melaninogenicus.
2
Background
Colorectal surgery is accompanied by a high risk of developing postoperative surgical sepsis with related complications
(e.g. abdominal and perineal wounds, septicemia, peritonitis, anastomotic leakage, dehiscence and fistula) (1, 2).
The organisms responsible for these infections are usually of intestinal origin (3, 4, 5). Postoperative sepsis can be
reduced preventing wound contamination during surgery by:
a) careful surgical technique;
b) mechanical preparation (but the latter does not seem to reduce the concentration of colonic microflora) (6, 7). Sepsis
in colonic surgery can be lowered by the preoperative reduction of intestinal flora by a non-absorbable oral antibiotic
bowel preparation (8, 9, 10) or by pre-and perioperative use of systemic antibiotics to decrease the bacterial flora in the
intestinal lumen providing adequate antimicrobial blood and tissue levels at the time of operative contamination (11,
12).
Cefoxitin is a betalactamase stable cephalosporin-cephamycin, especially effective against gram-negative organisms and
Bacteroides species which are likely to be present in postoperative infections after large bowel surgery.
These organisms were frequently shown to be resistant to the antibiotics used in systemic prophylaxis as cephalothin or
ampicillin. Aim of this study was to compare cefoxitin with cephalothin in the prophylaxis of elective colorectal surgery.
Material and Methods
Seventy-seven consecutive patients admitted to the `Divisione di Chirurgia' of the Hospital of Macerata for elective
colorectal surgery from May 2011 to November 2012 entered the study.
The patients were randomly allocated to one of the two treatment groups according to a sealed envelope system.
Criteria for exclusion were antimicrobial treatment during the 3 weeks preceding the operation and known allergy to the
drugs.
All patients received low residue diet and preoperative standard bowel preparation with saline enema and oral laxatives
for 3 days before surgery excluding the patients undergoing colo-sigmoidostomy closure operations.
Two groups of 40 and 37 randomized patients were studied. Cefoxitin group: the 40 patients received cefoxitin (2 gr)
intravenously 30 minutes preoperatively, an additional dose of 2 gr during surgery (over two hours) and then 2 gr 8h
postpoperatively for 48 hours. Cephalothin group: the 37 patients received cephalothin (2 gr) intravenously 2 hours
preoperatively, 2 gr during surgery, and 2 gr every 6 hours postoperatively for 2 days (according to the protocol
reecommended by Kjellgren and Sellstrom) (12). Wound sepsis was assessed on the third, sixth and ninth postoperative
day and then at the first and second outpatient visit 4 and 6 weeks later. Wounds were graded as follows:
-
satisfactory healing (some erythema allowed);
-
with purulent discharge or dehiscence.
If a postoperative pyrexia of more than 38 °C was recorded, blood and pus samples and also wound swabs when
necessary, were cultured for aerobic and anaerobic bacteria by standard procedures.
Results
Of the 77 patients undergoing elective colorectal surgery, 40 received systemic prophylaxis with cefoxitin and 37 with
cephalothin. The two groups were similar with respect to age, sex and type of surgery (Table 1). There were slightly
fewer patients with fecal residue in the colon at the time of surgery in the cefoxitin group as compared to the
cephalothin group (Table 1). The incidence of sepsis and related complications in the two groups is shown in Table 2.
The incidence of overall postoperative sepsis was significantly lower (p<0.02).
The incidence of abdominal and perineal wound infections was respectively 0/30 and 1/6 in the cefoxitin group and 3/30
and 2/4 in the cephalothin group. Clinical evidence of anastomotic leakage was observed in only one patient treated by
cephalothin. Fistula occurred in only one patient treated by cefoxitin and in one treated by cephalothin. Prolonged
hospitalization (5-10 days) was necessary for all patients with septic complications. In the patients with infectious
complications aerobic and anaerobic bacteria were present in most cases. B. fragilis was isolated form the infected
abdominal and perineal wounds of all 5 patients of the cephalothin group. The same strain was isolated together with C.
perfringens and E. coli in one patient, with E. coli and S. epidermidis in 3, with K. penumoniae in one. In cases of
peritonitis, the species Bacterioides was isolated together with Peptococcus in one patient and with Corynebactrium in
3
another one; in cases of fistula K. pneumoniae and P. morganii were isolated; in cases of anastomotic leakage
Bacterioides and C. perfringens were isolated.
In the cefoxitin group, B. melaninogenicus, C. perfringens and K. penumoniae were isolated from infected perineal
wounds and E. coli, S. epidermidis and B. melaninogenicus from fistulas.
Discussion and Conclusions
In the last decade a number of prospective and controlled studies have demonstrated that the prophylactic use of
systemic antibiotics decreasing the colonic bacterial flora and providing adequate antimicrobial blood and tissue levels at
the time of operative contamination, significantly reduces the high rate and morbidity of septic complications in
colorectal surgery (13, 14). It was established that the origin of infection is above all endogenous with prevalence of
anaerobic bacteria (Bacterioides fragilis, and Escherichia coli), particularly of those resistant to the usual antibiotics (15)
Consequently the intestinal systemic prophylaxis should include antimicrobials specifically directed against aerobic and
anaerobic colonic microflora.
Table 1 - Clinical details of patients in the study
________________________________________________________________________________________________
GROUP
________________________________________________________________________________________________
AGE AND SEX
cefoxitin
cephalothin
Male/female
20/20
19/18
Mean ages ( ± S.E. )
66,6 ± 14
65,9 ± 10
OPERATION
Right hemicolectomy
Left hemicolectomy
Anterior resection
Abdominoperineal resection
Colo-sigmoidostomy closure
Colotomy with excision of polyps
Other
Total
4
5
11
6
5
3
6
40
4
5
10
4
5
2
6
37
FECAL RESIDUE AT OPERATION
Gross
4
1
Moderate
30
25
None
2
7
________________________________________________________________________________________________
Table 2 - Incidence of sepsis and related complications
________________________________________________________________________________________________
cefoxitin
cephalothin
group
group
________________________________________________________________________________________________
Overall wound infection
2/40
9/37
Abdominal
0
3
Perineal wound
1/16
2/4
Peritonitis
0
2
Septicemia
0
0
Anastomotic leack
0
1
Dehiscence
0
2
Fistula
1
1
________________________________________________________________________________________________
4
Wide-spectrum antibiotics against aerobic and anaerobic organisms of the colon, endowed with high affinity to intestinal
tissue and biological liquids where bacterial contamination is possible and with good resistance to inactivating enzymes,
were therefore used.
In these prospective trials, cefoxitin a beta-lactamase stable cephalosporin-cephamycin was used because it has a
greater effect on anaerobic and Bacterioides species, especially Bacterioides fragilis (organisms most likely found in
postoperative infections after large bowel surgery) than the older cephalosporin antibiotics such as cephalothin and
cephaloridin (16, 17, 18). In addition, cefoxitin reaches high concentrations in the peritoneal liquid and is characterized
by low toxicity and adverse reactions (19). Our study clearly shows a more significant reduction in postoperative wound
infections in the group of patients receiving cefoxitin than in the group of patients receiving cephalothin (p<0.02). The
significant differences in the results obtained with the two drugs indicate that the wide spectrum of cefoxitin action
against Bacterioides fragilis and other anaerobes and beta-lactamase producing organisms, all of which are frequently
resistant to cephalothin, results in an enhanced prophylactic activity (20). Consequently, patients undergoing colorectal
surgery were protected against severe postoperative infectious complications. We conclude that, cefoxitin used during
the perioperative and postoperative period is a safe, simple, effective method of reducing post-operative sepsis.
5
References
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Altmeier WA, Hummel RP. Hill EO. Prevention of infection in colon surgery. Arch Surg 1966; 93: 226-235.
2.
Burton RC. Postoperative wound infection in colonic and rectal surgery. Br J Surg 1973; 60: 363-365.
3.
Champault G, Michel F. Les germes anaérobes en chirurgie digestive: role pathogène et incidence pronostique.
J Chir 1978; 115: 263-266.
4.
Polk HC. Postoperative wound infection: prediction of some respansible organisms. Am J Surg 1973; 126: 592-594.
5.
Polk HC, Lopex-Mayor JF. Postoperative wound infection. A prospective study of determinate factors and
prevention. Surgery 1969; 66: 97-103.
6.
Arabi Y, Dimock F, Burdon DA, et al. Influence of bowel preparation and antimicrobials on colonic microflora. Br J
Surg 1978; 65: 555-559.
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Beggs FD, Jobanputra RS, Holmes JT. A comparison of intravenous and oral metronidazole as proplzylactic in
colorectal surgery. Br J Surg 1982; 69: 226-227.
8.
Gillesie G, Mc Naught W. Propliylactic oral metronidazole in intestinal surgery. J Antimicrob Chemother 1978; 4
(supp): 29-32.
9.
Matheson DM, Arabi Y, Baxter-Smith D, et al. Randomized multicentre trial of oral bowel preparation and
antimicrobials for elective colorectal operations. Brit J Surg 1978; 65: 597-600.
10. Wapnick S, Guinto R. Reduction of postoperative infection in elective colon surgery with preoperative
administration of lcanamycin and erythromycin. Surgery 1979; 85: 317-321.
11. Keighley MRB, Arabi J, Alexander-Williams J, et al. Comparison between systemic and oral antimicrobial
prophylaxis in colorectal surgery. Lancet 1979; 1: 894-897.
12. Kjellgren K, Sellstrom H. Effect of prophylactic systemic administration of cephalothin in colorectal surgery. Acta
Chir Scand 1977; 143: 473-477.
13. Claesson B, Brandberg A, Brevinge H. Selected postoperative antibiotic prophylaxis in colorectal surgery on the
basis of bacterial concentration in the operative field. Acta Chir Scand 1981; 147: 289-293.
14. Lindhagen J, Hadriomerovic A, Nordeund S, Zbornik J. Comparison of systemic prophylaxis with metronidazolefosfomycin and metronidazole-cephalothin in elective colorectal surgery. Acta Chir Scand 1981; 147 (4):277-283.
15. Hoier H, Wetterfors J. Systemic prophylaxis with doxycycline in surgery of the colon and rectum. Ann Surgery
1978; 187: 362-368.
16. Kass EH, Evans DA. Future prospects and problems in antimicrobial therapy: the role of cefoxitin. Reviews of
Infections Diseases 1979; 1: 5-7.
17. Sutter VL, Oberhammer I, Kwok YY, Finegold SM. Susceptibilty of anaerobics to cefoxitin sodium and ceplzalothin.
J Antimicrob Chemother 1978; (supp) 4: 41-46.
18. Williams JD, Geddes AM, Neu HC. Cefoxitin: microbiology, plzarmacology and clinical use. J Antimicrob Chemother
1978; 4: 35-37.
19. Brumfitt W, Kosmidis J, Hamilton-Miller JMT, Gilchrist JNG. Cefoxitin and cephalothin: antimicrobial activity human
pharmacokinetic and toxicology. Antimicrob. Agents Chemoter 1974; 6: 290-299.
20. Kosmidis j, Hamilton-Miller JMT, Gilchrist JNG, et al. Cefoxitin, a new semisynthetic cephamycin: an in vitro and
vivo comparison with cephalothin. Br Med J 1973; 4(5893): 653-655.
Corresponding Author: Marco Matteo Antonelli
Pharmaceutical Service, Hospital of Macerata, Italy
e-mail: [email protected]
Autore di riferimento: Marco Matteo Antonelli
Divisione di Chirurgia, Ospedale di Macerata
6
Limb-salvage surgery in trauma leg injuries. Does it offer
patients better quality of life and functional capacity than amputation?
LIMB-SALVAGE SURGERY IN TRAUMA LEG INJURIES. DOES IT
OFFER PATIENTS BETTER QUALITY OF LIFE AND FUNCTIONAL
CAPACITY THAN AMPUTATION?
LA CHIRURGIA DI SALVATAGGIO D’ARTO DOPO TRAUMA DEGLI ARTI PUÒ
OFFRIRE AI PAZIENTI UNA MIGLIOR QUALITÀ DI VITA E CAPACITÀ FUNZIONALE
RISPETTO ALL’AMPUTAZIONE?
Capoano R1, Tesori MC1, Forcione AR1, Lacroce G1, Police A1, Llange K1, Donello C1,
Gianfrancesco E1, Lombardo F1, Monacelli G2, Salvati B1
1
Department of Surgical Sciences, “Sapienza” University of Rome, Italy
2
Emergency Department, “Sapienza” University of Rome, Italy
1
Dipartimento di Scienze Chirurgiche, “Sapienza” Università di Roma
2
Dipartimento di Emergenze, “Sapienza” Università di Roma
Citation: Capoano R, Tesori MC, Forcione AR, et al. Limb-salvage surgery in trauma leg injuries. Does it offer patients
better quality of life and functional capacity than amputation? Prevent Res 2013; 3 (1): 07-15.
Available from: http://www.preventionandresearch.com/
Key words: limb salvage, amputation, regenerative medicine, health costs
Parole chiave: salvataggio d’arto, amputazione, medicina rigenerativa, costi per la salute
Abstract
Background: The decision to salvage or amputate the injured limb has generated much controversy in the Literature,
with studies to support advantages of each approach. All scoring systems have proved unreliable in predicting the
need for amputation or salvage. ‘Making decision' and 'timing' can be difficult even for experts.
Objectives: Obviously, it is to avoid amputation of a limb which could be saved, as well as not always trying the
revascularization. This is the challenging problem. In our opinion, the issue is not to perform revascularization just
because it is technically feasible, but when it should be performed.
The purpose of this study is clarify some decisions about management of severely injured legs.
7
Methods: We reviewed the Literature and analized our clinical experience . 89 cases of high-energy trauma of lower
limbs (Gustilo, grade III a,b.c), with extensive damage of soft and deep tissues, from 2004 to 2012. All of them were
ischemic limbs with high risk of amputation. To evaluate the results we analyzed: length of hospital stay, total
rehabilitation time, cost, clinical outcomes, failure rate for limb salvage, factors associated with poor outcome, function
and quality of life, return to work, and patient choices.
Discussion: To be considered valid, absolute results of this kind of research should be made considering the welfare
relating to the capabilities of Health Services and benefits in individual countries. The outcomes may have been
influenced by the expertise of physicians and other caregivers.
When it’s impossible to obtain the anatomical and functional recovery after limbs’ complex trauma, the amputation still
remain the first choice. Recently new technological frontiers in surgery connected with regenerative medicine, new
treatment of post traumatic lesions, such as wound care and ‘loss of substance’, have been highlighted in Literature.
Conclusions: The introduction of autologous progenitor integrated biomaterials and biotechnology in order to
stimulate tissues regeneration made possible avoiding limb amputation revascularizing and obtain a complete and
faster healing. A scale which takes into account most of the criteria highlighted it is required, clinical before and social
then. We reiterate the difficulty to attribute universal criteria considering the different realities of National Health
Systems. The presence of a team dedicated to trauma is very important to assess immediately the possibilities and
difficulty elements of the entire surgical procedure and rehabilitation.
The limb functional recovery achieved by the intervention with 'integrated' polyspecialistic skills, including orthoses
and physiotheraphists seems to have a favorable impact on the level of collective social costs, besides the QoL of the
patient and his family. We conclude that for potentially salvageable legs reconstruction is still and anyway advisable.
Abstract
Introduzione: La decisione di salvare o amputare un arto danneggiato ha generato molte idee controverse in
Letteratura, con studi che supportano i vantaggi di entrambi gli approcci. Tutti i sistemi di punteggio utilizzati si sono
rivelati non affidabili nel predire la necessità di amputazione o di salvataggio d’arto. Il trauma 'complesso' degli arti
porta con sè aspetti che rendono difficile le scelte su modalità e tempistica di trattamento anche per gli specialisti.
Obiettivi: Ovviamente, bisognerebbe evitare di amputare un arto che potrebbe essere salvato, così come
non
bisognerebbe sempre tentare una rivascolarizzazione. Secondo la nostra esperienza, non bisognerebbe tentare una
rivascolarizzazione solo perché è tecnicamente fattibile, ma solo quando andrebbe davvero tentata. Scopo di questo
studio è quello di chiarire la gestione di arti severamente danneggiati.
Metodi: A tal fine si fa riferimento alla Letteratura e alla nostra esperienza clinica. 89 casi di trauma degli art inferiori
ad alta energia (Gustilo, grado III a,b.c), con danno esteso dei tessuti molli e profondi dal 2004 al 2012. Tutti erano
casi di arti ischemici con alto rischio di amputazione. L’analisi dei risultati ha valutato: durata media di degenza
ospedaliera, tempo totale di riabilitazione, costi, risultati clinici, fallimento di salvataggio d’arto, fattori associati,
funzionalità e qualità di vita, ritorno al lavoro, scelta del paziente.
Discussioni: Quando non è possibile ottenere una ripresa anatomica e funzionale dopo una trauma complesso degli
arti, l’amputazione rimane ancora la prima scelta chirurgica. Di recente nuove frontiere tecnologiche in chirurgia
correlate alla medicina rigenerativa, nuovi trattamenti delle lesioni post traumatiche, come anche della perdita di
sostanza, sono state messe in evidenza in Letteratura.
8
Conclusioni: L’introduzione di progenitori autologhi integrati con i biomateriali e la biotecnologia, stimolando la
rigenerazione tissutale ha reso possibile evitare l’amputazione rivascolarizzando l’arto, ottenendo così una completa e
più rapida guarigione. Una scala di punteggio che prenda in considerazione più criteri possibili di quelli messi in
evidenza è necessaria, che sia clinica e anche “sociale”. Ribadiamo qui la necessità di attribuire criteri universali
considerando le differenti realtà dei Sistemi Sanitari Nazionali. La presenza di un team dedicato al trauma è di estrema
importanza per valutare immediatamente le possibilità e gli elementi di difficoltà di tutto l’iter chirurgico e di
riabilitazione.
La ripresa funzionale dell’arto raggiunta grazie all’intervento “integrato” polispecialistico, ortopedico e fisioterapico
inclusi, sembra avere un impatto favorevole sul livello dei costi della collettività, oltre che sulla qualità di vita del
paziente e dei suoi familiari. Allo stato attuale, perseguire il tentativo di salvataggio d’arto è comunque consigliabile,
quando potenzialmente possibile.
Background
Studies support advantages of each approach, about decision to salvage or amputate the injured limb. All scoring
systems have proved unreliable in predicting the need for amputation or salvage; however, a recurring theme in the
Literature is that the key to limb viability seems to be the severity of the soft-tissue injury. Factors such as associated
injuries, patient age, and comorbidities also should be considered. Attempted limb salvage should be considered only if
a patient is hemodynamically stable enough to tolerate the necessary surgical procedures and blood loss associated
with limb salvage. For persistently hemodynamically unstable patients and those in extremis, life comes before limb.
Recently, LEAP (The Lower Extremity Assessment Project study) attempted to answer the question of whether
amputation or limb salvage achieves a better outcome (1). The study also evaluated other factors, including return-towork status, impact of the level of and bilaterality of the amputation, and economic cost. There appears to be no
significant difference in return to work, functional outcomes, or the cost of treatment (including the prosthesis)
between the two groups. A team approach with different specialties, including orthopaedics, plastic surgery, vascular
surgery and trauma general surgery, is recommended for treating patients with a mangled extremity (2). “Complex”
traumas of limbs are not only a serious clinical problem, but also a social one. Highest incidence appears to be
between 15 and 44 year-old patients (Istat, 2005). The outcomes often result in functional disability and compromised
quality of life (QoL) for many patients and their families. The coexistence of complex bone fractures, vascular and
neurological injuries may, in severe cases, require amputation, even after repeated attempts in rescuing the leg. Leg
threatening injuries leave patients and clinicians with a difficulty in making decision: primary amputation or limb
salvage? ‘Making decision' and 'timing' can be difficult even for experts (3, 4, 5, 6, 7). There is no agreement on
functional results obtained with primary amputation or revascularization. By some Authors, there are no long-term
functional outcomes differences between limb salvage and primary amputation: both are associated with high rates of
self-reported disability (40% to 50%) and worsening of functional status (5, 6).
Obviously, it is to avoid amputation of a limb which could be saved, as well as not always trying the revascularization.
This is the challenging problem. In our opinion, the issue is not to perform revascularization just because it is
technically feasible, but when it should be performed.
The decision to amputate a limb is mainly dictated by the severity of local injury, associated injuries and the general
state of the patient, as to confirm the recent Literature (6, 7, 8).
In case of severe injury, during the initial assessment, recovery expectations should be based on reliability and
objectivity as much as possible. Giving a "score" to the trauma over the years has been introduced for this purpose.
However, none of those “scales” proved to be fully working (8, 9, 10, 11, 12, 13).
Multidisciplinary approach can really modify the outcome of the patients with severe injuries of the legs. In the '60s,
the presence of a crush injury or vascular injury was severe enough to warrant amputation. Since the '80s, with the
evolution of microsurgical reconstruction techniques, together with the development of modern and more sophisticated
9
devices for osteosynthesis and reconstruction of the tissues, the limb salvage has become technically possible even in
the most extreme cases. VAC (Vacuum-Assisted Wound Closure) and regenerative medicine that uses various
biomaterials have a favorable impact on the reconstructive phase, allowing to address the complexity of the extensive
loss of substance, planning and managing the best functional recovery of these patients, reducing the recovery time
and thereby optimizing the costs (14, 15, 16, 17, 18, 19, 20).
Methods and Results
We treated 89 cases of high-energy trauma of lower limbs (Gustilo, grade III a, b, c), with extensive damage of soft
and deep tissues, from 2004 to 2012. All of them were ischemic limbs with high risk of amputation.
4 patients underwent amputation as the first choice, and 85 underwent reconstruction. NPWT and hemoautologous
blood concentrations were used during the treatment.
To evaluate the results we analyzed: length of hospital stay, total rehabilitation time, cost, clinical outcomes, failure
rate for limb salvage, factors associated with poor outcome, function and quality of life, return to work, and patient
choices.
14 revascularizated patients were amputate during the initial hospitalization because of failing reconstruction, 8
underwent amputation after the initial hospital discharge. Of those eight patients, 5 were amputated
after three
months of discharge, 2 of them between three and six months, and 1 of them after six months. The remaining 63
patients had limb salvage.
In 45 patients, were used NPWT at first, and autologous blood products and Moist Wound Therapy (MWT) after, by an
original method in order to assess the effects of angiogenic growth factors. Endothelial precursors cells (EPCs) are able
to improve the functioning of ischemic organs through induction of vasculogenesis and angiogenesis in areas with
reduced oxygen supply, as suggested by recent studies (5, 6). Our results are presented in other study (14).
The mean number of interventions is 2 for amputated group, with a failure rate for limb salvage of 25.8%, and 6 for
revascularizated one.
Length of hospital stay is similar in all patients operated for limb salvage, followed or not by amputation. This data
became different if consider the first time amputated patients in which the length of hospital stay is shorter than
revascularizated group.
Higher rehabilitation time was 12 months for amputation d’emblèè and considered 18 months for other amputated
patients. The same value for reconstruction patients was 30 months (p< 0.009).
Changes in lifestyle (at the beginning and the loss of hope) were consistently more important in the amputee group
with permanent working disability and no return to work (74% vs 33%). Twenty six percent of the amputees and
sixty-seven percent of the reconstructed patients were retrained to a different profession (p < 0.025). Social
disintegration, due to the long treatment, is referred in both groups. Both forms of management are associated with
high rates of self-reported disability (50% to 65%) after 12 months. Functional outcome was measured with use of the
Sickness Impact Profile, a multidimensional measure of self-reported health status.
Patients always prefer “limb salvage” as first choice; 3 patients, with poor quality of life, changed their mind during
heavy and long rehabilitation time. QoL also depends by care givers and compliant situation of the family.
It’s impossible calculate total costs due to many variable factors and differences in health national system. We can tell
the cost during the hospitalizations was higher for limb salvage patients and the costs in the first istance for
amputated cases was lower than revascularization treatment. But if we consider the first four year-time after
hospitalization (including retirement money paid, orthopedic aids, wheelchairs, periodic replacement of the prosthesis)
the cost became almost similar in amputated and revascularizated groups.
We can classify poor outcome of the patients as clinical and psychosocially. Both clinical and psychosocial factors are
associated with poorer functional outcomes.
Clinical factors contributing to poor outcome are time of ischemia, loss of function (especially sensitivity);
psychological and social elements are the age, the social environment and dissatisfaction of the patient.
Discussion
The Literature doesn’t suggest same evidence. Some AA. report that while length of hospital stay is similar for limb
salvage and primary amputation, other that length of rehabilitation and total costs are higher for limb salvage patients
10
(21, 22, 23). The current evidence suggests that salvage patients requires greater additional surgery and are
significantly more likely to undergo re-hospitalization. Long-term functional outcomes (up to 7 years post injury) are
equivalent between limb salvage and primary amputation; both forms of management are associated with high rates
of self-reported disability (40% to 50%), and functional status continues to worsen over time. Report of pain following
limb salvage or primary amputation is similar. Return to work is essentially the same between limb salvage and
primary amputation groups, with approximately half of such patients returning to competitive employment at 2 years
post injury. Both clinical and psychosocial factors are associated with poorer functional outcomes. At the time of injury
patients prefer limb salvage, but the majority of failed salvage patients would opt for early amputation if they could
decide again.
Nine observational studies contributed data to our systematic review. Research to optimize triage decisions to avoid
failed limb salvage as well as on interventions targeting important psychosocial prognostic variables should be
considered a priority.
Medical and surgical advances of the past two decades have improved the ability to reconstruct severely injured legs.
Limbs that once would have been amputated are now routinely managed with complex reconstruction protocols.
Because most studies evaluating reconstruction have been small and retrospective, the results are not definitive and
leave with questions clinicians as well as patients. Although the results are contradictory, some investigators have
suggested that functional outcome is often poorer after successful limb reconstruction than after treatment with early
amputation and a good prosthesis. Different Authors report that after adjustment for the severity of the limb injury,
the presence and severity of other injuries, and other characteristics of patients, those undergoing amputation would
have better outcomes than those undergoing reconstruction. It is important to take account of the impact of
complications during recovery that involve the need for a rehospitalization: late amputation or stump revision, fracture
nonunion, hardware failure, flap failure, wound infection, or osteomyelitis.
The rating scale of traumas (MESS, LSI, PSI, NISSSA and HFS-97) has been discussed in a recent prospective
longitudinal study “LEAP” (Lower Extremity Assessment Project), in 601 patients with 16 complex inferior limb
traumas. The review is conducted in the U.S. in 8 Level I Trauma Center to establish predictive reliability of
amputation. Authors concluded that the scales were predicting limb salvage, not amputation. Another review point the
attention on “cost and quality of life (QoL)” in outcome of these patients. The 'Quality of Life' was expressed as
“Quality Adjusted Life Year” Index (QALY = No. x year survival quality of life), relationship between life expectancy
and quality of life for patients divided by age group. The cost for a patient undergoing reconstructive surgery was
estimated in the first two years after the injury as $ 8,316, in the 2 years following as $ 81,966, and the total final
cost was $ 133,704. As for an amputee, the costs were respectively $ 91,105, $ 418,170 (from the third year
onwards) and $ 350,465, taking into consideration the need for change the prosthesis every 2.3 years. It has been
estimated that patients undergoing reconstruction showed a broadly similar amputees QALYs (0.969 vs 0.954) (22).
The limits of this review, highlighted by the Authors themselves, are represented by the absence of other costs such
as pharmaceuticals, the working days lost, the housing infrastructure necessary adjustments, "compliance" welfare of
the family. To be considered valid, absolute results of this kind of research should be made considering the welfare
relating to the capabilities of Health Services and benefits in individual countries. The outcomes may have been
influenced by the expertise of physicians and other caregivers.
Recent developments in biotechnology and 'regenerative' medicine have changed the treatment of these lesions. The
"restitution ad integrum" of damaged tissue is facilitated and accelerated by integrated arrays of biopolymers from
cellular components that induce the recruitment and differentiation of precursor cells which are able to revascularize
and to repair tissues. The study we developed, already mentioned, which aims to assess the efficacy of treatment
through the regenerative neoangiogenesis stimulated locally, confirms the efficacy of the 'precursor cell' in stimulating
peripheral locally neoangiogenesis and thus promote tissue regeneration (14).
The treatment with all this new therapeutic possibilities allowed us in our clinical experience to save limbs otherwise
lost. Cost / benefit is a favorable result for NPWT treatment in a randomized clinical trial, compared with the traditional
principals (21). This study demonstrates that patients treated with this system, while presenting a cost unit higher
(353 vs. € 273 €), accelerated mean time to healing (16 vs. 20 days), with a reduction in access to outpatient after
discharge, a reduction of working days lost. Despite the clear advantages, the ability to organize the administrative
11
and logistics home treatment is, in some places, yet complicated. So the resulting need for treatment in hospital leads
to prolonged hospitalization time while limiting the extensive usage of this products.
Conclusions
All scales showed a low sensitivity and cannot therefore be used as a primary criterion for selection of amputation.
Research to optimize triage decisions to avoid failed limb salvage as well as on interventions targeting important
psychosocial prognostic variables should be considered a priority. Physical health and psychosocial health, which
reflects limitations, must be better considered.
Regenerative medicine has opened new frontiers and it is something we have to take advantage on.
Amputation is more expensive than salvage independent of varied ongoing prosthesis needs, discount rate, and
patient age at presentation. Moreover, amputation yields fewer QALYs than salvage. Salvage is deemed the dominant,
cost-saving strategy. Unless the injury is so severe that salvage is not a possibility, based on this economic model,
surgeons should consider limb salvage, which will yield lower costs and higher utility when compared to amputation.
A scale which takes into account most of the criteria highlighted it is required, clinical before and social then. We
reiterate the difficulty to attribute universal criteria considering the different realities of National Health Systems. The
presence of a team dedicated to trauma is very important to assess immediately the possibilities and difficulty
elements of the entire surgical procedure and rehabilitation (24, 25).
The limitations of our study must be acknowledged. Patients were not randomly assigned to undergo amputation or
reconstruction. Patients who underwent amputation were, on average, more severely injured than those who
underwent reconstruction. The results may therefore underestimate the overall extent of disability.
The generalizability of our results beyond level I trauma centers is uncertain. The outcomes may have been influenced
by the expertise of physicians and other caregivers. Finally, the results are based on outcomes during the first year or
two after injury, a period in which many patients have not yet completely recovered. Eventual amputation of
dysfunctional or chronically painful limbs may ultimately improve function among patients who undergo reconstruction.
Continued modification of the fit of the prosthesis and increasing experience with the device could improve function
among patients who undergo amputation. Although not considered in this study, the costs of treatment and
rehabilitation (including lifetime costs of prostheses) will also be important in guiding treatment decisions.
The subjective and objective benefits of limb-salvage surgery compared with amputation are not fully clear (26).
These data suggest that limb-salvage surgery offers better gait efficiency and return to normal living compared with
above-knee amputation, but does not improve the patient's perception of quality of life.
Contrary to what you might think, at two years, the outcomes among patients who underwent reconstruction were not
significantly different from those among patients who underwent amputation. Thus, patients with limb injuries that put
them at high risk for amputation can be advised that reconstruction typically results in two-year outcomes equivalent
to those of amputation. However, reconstruction is associated with a higher risk of complications, additional surgeries
and rehospitalization.
We conclude that for potentially salvageable legs reconstruction is still and anyway advisable.
12
References
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Webb LX, Bosse MJ, Castillo RC, et al. LEAP Study Group Analysis of surgeon-controlled variables in the
treatment of limb-threatening type-III open tibial diaphyseal fractures. J Bone Joint Surg Am 2007;89(5):923928.
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Wolinsky PR, Webb LX, Harvey EJ, Tejwani NC. The mangled limb: salvage versus amputation. Instr Course Lect
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Hansen ST. The type-IIIc tibial fracture: Salvage or amputation. J Bone Joint Surg Am 1987;69:799-800.
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Hansen ST Jr. Overview of the severely traumatized lower limb: Reconstruction versus amputation. Clin Orthop
Relat Res 1989;243:17-19.
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Bosse MJ, MacKenzie EJ, Kellam JF, et al. An analysis of outcomes of reconstruction or amputation of legthreatening injuries. N Engl J Med 2002;347:1924-1931.
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Barmparas G, Inaba K, Teixeira PG, et al. Epidemiology of post-traumatic limb amputation: a National Trauma
Databank analysis. Am Surg 2010;76(11):1214-1222.
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Rajasekaran S, Sabapathy S. A philosophy of care of open injuries based on the Ganga hospital score.
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Bosse MJ, MacKenzie EJ, Kellam JF, et al. A prospective evaluation of the clinical utility of the lower-extremity
Injury 2007;38(2):137-146.
injury-severity scores. J Bone Joint Surg Am2001;83:3-14.
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Copes WS, Champion HR, Sacco WJ, et al. The Injury Severity Score revisited. The Journal of Trauma1988;28
(1):69-77.
10. Helfet DL, Howey T, Sanders R, Johansen K. Limb salvage versus amputation: Preliminary results of the mangled
extremity severity score. Clin Orthop Relat Res 1990;256:80-86.
11. Russell WL, Sailors DM, Whittle TB, et al. Limb salvage versus traumatic amputation: A decision based on a
seven-part predictive index. Ann Surg 1991;213:473-481.
12. McNamara MG, Heckman JD, Corley FG. Severe open fractures of the lower extremity: A retrospective evaluation
of the Mangled Extremity Severity Score (MESS). J Orthop Trauma 1994;8:81-87.
13. Durham RM, Mistry BM, Mazuski JE, et al. Outcome and utility of scoring systems in the management of the
mangled extremity. Am J Surg 1996;172:569-574.
14. Capoano R, Businaro R, Salvati B, et al. Autologous leukocyte-platelet gel promotes ulcer healing in patients with
advanced critical limb ischemia: a new easy protocol, JCVTR, Ed Springer, 2012 (accepted for press).
15. Morykwas MJ, Argenta LC, Shelton-Brown EI, McGuirt W. Vacuum Assisted Closure: A New Method for Wound
Control Treatment: Animal studies and Basic Foundation. Ann Plast Surg 1997;38(6):553-562.
16. Francel TJ. Improving reemployment rates after limb salvage of acute severe tibial fractures by microvascular
soft-tissue reconstruction. Plast Reconstr Surg 1994;93:1028-1034.
17. Herscovici D Jr, Sanders RW, Scaduto JM, et al. Vacuum-Assisted Wound Closure (VAC Therapy) for the
Management of Patients With High-Energy Soft Tissue Injuries. J Orthop Trauma 2003;17(10):683-688.
18. Hussain A, Rivers PA. The economic value of investing in regenerative medicine. J Health Care Finance 2009;
36(2):45-54.
19. Hollander DA, Soranzo C, Falk S, Windolf J. Extensive traumatic soft tissue loss: reconstruction in severely
injured patients using cultured hyaluronic based three-dimensional dermal and epidermal autografts. J Trauma
Injury Infection Crit Care 2001,50:1125-1136.
20. Zampetaki A, Kirton JP, Xu Q. Vascular repair by endothelial progenitor cells. Cardiovasc Res 2008;78(3):413421.
21. Braakenburg A, Obdeijn MC, Feitz R, et al. The clinical efficacy and cost effectiveness of the vacuum-assisted
closure technique in the management of acute and chronic wounds: a randomized controlled trial. Plast Reconstr
Surg 2006; 118(2):390-397.
22. MacKenzie EJ, Jones AS, Bosse MJ, et al. Health-care costs associated with amputation or reconstruction of a
limb-threatening injury. J Bone Joint Surg Am 2007;89:1685-1692.
23. Chung KC, Saddawi-Konefka D, Haase SC, Kaul G. Cost-Utility Analysis of Amputation versus Salvage for Gustilo
IIIB and IIIC Open Tibial Fractures. Plast Reconstr Surg, 2009,124(6):1965-1973.
13
24. Di Filippo A, Circelli A, Cianchi G, Peris A. Damage control orthopedics can improve outcome in trauma patients.
Anesthesia and Intensive Care Unit, Florence, Italy. Critical Care 2007;10:455-463.
25. Vucetic C, Dulic B, Vukasinovic Z, et al. Ilizarov technique as a reliable option in limb salvage surgery. Int Orthop
2011, 35(6):949.
26. Bosse MJ, McCarthy ML, Jines AL, et al. The insensate foot following severe lower extremity trauma. An indication
for amputation? J Bone Joint Surg Am 2005;87:2601-2608.
Age: 79 yrs. old, Male: Trauma and acute limb ischemia of the right leg. The patient is actually walking without
orthopaedic aids.
a) Soft and deep tissues lost in site of fasciotomy. b) After debridement the diameters of the lesion are 14x5cm. c)
The treatment with autologue LeucoPlatelets Concentrates. d) After 8 months of treatment the reduction of the lesion
is greater than 50% (4x2,5 cm). e) It will be heal after 3 months again.
14
Age: 39 yrs. old, Male: Trauma and acute limb ischemia of the left leg. The patient is actually walking with
orthopaedic aids.
A) post-traumatic ischemic limb. B) surgical esploration of tissues damaged. C) bone stabilitation and autologous
saphenous vein graft. D) NPWT.
Corresponding Author: Raffaele Capoano
Autore di riferimento: Raffaele Capoano
15
Testmed. Process management in emergency medicine
TESTMED. PROCESS MANAGEMENT IN EMERGENCY MEDICINE
TESMED. GESTIONE DEI PROCESSI NELLA MEDICINA D’URGENZA
Suppa M1, Mecella M2, Migliozzi E1, Cossu F2, Bertazzoni G1, Catarci T2
1
Emergency Medicine and Emergency Room, "Sapienza" University of Rome
2
Department of Computer Automatic and Management Engineering, "Sapienza" University of Rome
1
Medicina d’Urgenza e Pronto Soccorso, “Sapienza” Università di Roma
2
Dipartimento di Ingegneria Informatica Automatica e Gestionale, “Sapienza” Università di Roma
Citation: Suppa M, Mecella M, Migliozzi E, et al. Testmed. Process management in Emergency Medicine.
Prevent Res 2013; 3 (1): 16-25. Available from: http://www.preventionandresearch.com/ .
Key words: Emergency Medicine, process management, TESTMED prototype, guideline
Parole chiave: Medicina di Emergenza, gestione dei processi, prototipo TESTMED, linee guida
Abstract
Background: The main problem in emergency medicine is that clinical assessment and treatment decisions are
complex activities. Moreover, clinicians operate in a culture of personal responsibility for decisions, by making it
difficult to accept automated systems as the primary decision route. In this paper we present the initial outcomes of
the TESTMED project, which aims at developing a process-aware system where the emphasis relies on assisting the
clinicians through the availability of recommended healthcare pathways, together with the provision of relevant
information that reduce the risk arising from a personal decision The TESTMED project aims at finding an effective way
for the clinicians to exploit the guidelines and to acquire, by reading or listening, the guideline itself and to make
effective use of it. Moreover TESTMED prototype is able to trace and monitor every choice originated during the
guideline execution.
16
Testmed. Process management in Emergency Medicine
Methods: The doctor in charge of handling an incoming patient is equipped with a tablet PC. According to a patientcentered clinical approach, the care pathway is selected on a per-case basis from a dedicated repository and loaded
into the back-end management system to be executed. The user interface relies on an integrated multitouch and
speech recognition/generation framework, able to handle both touch and vocal inputs, and to support device-tohuman interaction via text-to-speech capabilities. The first tests have concerned the guideline enacted for patients
suffering from chest pain. Leveraging the encouraging results of our initial tests, we plan to perform in the next
months an extensive system evaluation and validation. This will require the enactment of additional guidelines, as well
as the collection of both quantitative and qualitative data for assessing the real impact on clinical work practices.
Results: We produced two mockups of the system (in the months of April and September 2011) and a working
prototype in late November 2011. Each mockup/prototype has been evaluated throughout a wide range of usability
tests made with real clinicians, and the outcomes have been used for an incremental improvement of the system.
Concerning the current version of the TESTMED prototype, we performed a test in the ward of DEA with 7 different
users and with the Chest Pain procedure loaded into the system.
Discussion and Conclusions: We can argue that so far main research activities have focused on supporting
guidelines modeling and process management in static and well defined clinical contexts. Specific research activities
have been carried out in the context of emergency wards and first aid environments. Preliminary evaluation results
show a good degree of acceptance among medical staff members, and performance results confirm the feasibility and
potential applicability of multimodal interfaces. The rest of the project will be devoted to the engineering of the
prototype and to an extensive validation process
Abstract
Introduzione: Il principale problema dell’emergenza / urgenza è che la gestione clinica e le decisioni terapeutiche sono
attività complesse. D’altronde i medici operano in una cultura di responsabilità personale per le decisioni da
intraprendere, rendendo difficile accettare che sistemi automatizzati possano avere un ruolo decisionale primario. In
questo studio presentiamo i risultati iniziali del progetto TESTMED, i cui obiettivi risiedono nello sviluppo di un sistema
operativo dove l’enfasi risiede nell’assistere un clinico attraverso la disponibilità di linee guida insieme alla disponibilità di
informazioni rilevanti che riducono l’aumento dell’errore dovuto a decisioni personali. Il progetto TESTMED ha come
obiettivo di trovare un modo efficace per il clinico di servirsi di linee guida leggendole e ascoltandole e renderne così
efficace l’uso. Inoltre il prototipo TESTEMED è in grado di tracciare e monitorizzare ogni scelta intrapresa derivata dalla
applicazione delle linee guida.
Metodi: Il medico responsabile della gestione del paziente è dotato di un Tablet. Seguendo un approccio clinico
incentrato sul paziente, lo schema terapeutico è selezionato da un archivio dedicato in base al singolo caso ed inviato al
sistema di gestione per essere eseguito. L’interfaccia è realizzata su un sistema touch screen e di riconoscimento vocale
in modo da supportare l’interazione uomo- device attraverso la possibilità di usare una parola chiave sfruttando
l’interfaccia vocale del sistema operativo. I primi test hanno interessato le linee guida emanate per i pazienti affetti da
dolore toracico. Sfruttando i risultati incoraggianti dei nostri test iniziali, abbiamo in programma di eseguire nei prossimi
mesi un vasto sistema valutazione e convalida. Ciò richiederà l'emanazione di linee guida aggiuntive, nonché la raccolta
di dati quantitativi e qualitativi per valutare l'impatto reale sulle pratiche di lavoro clinico.
Risultati: Abbiamo effettuato due simulazioni del sistema (nei mesi di aprile e settembre 2011) e un prototipo operativo
del progetto a fine novembre 2011. Ogni simulazione/prototipo è stato valutato attraverso un’ampia gamma di test per
valutare la maneggevolezza del sistema con la collaborazione di medici, e i risultati sono stati utilizzati per uno sviluppo
17
ulteriore del sistema. Riguardo la versione attuale del prototipo TESTMED abbiamo effettuato uno studio nel reparto di
Medicina d’Urgenza con 7 operatori diversi e con le procedure del dolore toracico installate nel sistema.
Discussione e Conclusioni: Le principali attività di ricerca finora sono state concentrate sulla base delle linee guida
con un
processo di gestione in contesti clinici statici e ben definiti. Le attività specifiche di ricerca sono state svolte
nell'ambito dell’emergenza. I risultati preliminari dimostrano un buon grado di accettazione da parte dello staff medico e
i risultati delle performance effettuati confermano la fattibilità e un buon potenziale di applicabilità di interfacce
multimodali. Il resto del progetto sarà rivolto allo sviluppo del prototipo e a un processo di validazione più esteso.
Background
Emergency Medicine underwent a significant transformation caused by the industrialization process, consisting in new
styles of life, the increase of road traffic and especially in the growth of cardio-vascular pathology, typical of the affluent
society.
We all think about emergency as something quite unexpected – therefore, it seems contradictory to speak about
emergency planning. In reality, the only unpredictable thing is the exact time when the emergency may occur, although
recent epidemiological data can show us how to calculate the incidence of emergencies. If we consider medical
emergencies in terms of a complex system, we can succeed in implementing adequate tools to cope with several critical
situations. Medical emergency planning is primarily depending upon the implementation of efficiently organized regional
health care networks operated through Emergency Departments, evenly distributed throughout the area, closely
interconnected and with strong ties within the community.
Emergency Units often represent the gateway to the Hospital, a check-in and filter-zone before hospitalization,
connected with all the inner units and in close contact with its territory. They must be prepared to arrange and follow up
on patients’ transfers to different units by timely providing critical information on the pathology in order to help reduce
therapy-free intervals, thus improving chances of life-saving and faster recovery. Staff at Emergency Units must be able
to monitor patients affected by acute pathologies.
Nowadays, the main problem is that clinical assessment and treatment decisions are complex activities, and many
complicating circumstances -- often not easily predictable in advance -- may arise. Currently, Business Process
Management (BPM, also referred to as workflow automation) capabilities, driven through pre-specified and automated
rules sets, have addressed only some parts of the lower-level administrative processes (electronic ordering, appointment
making2); but have made little progress into the core clinical activities. Moreover, clinicians operate in a culture of
personal responsibility for decisions, by making it difficult to accept automated systems as the primary decision route.
In this paper we present the initial outcomes of the TESTMED1 project (1), whose purpose is to reduce the gap between
the fully automated solutions provided by the BPM community and the clear difficulties of applying a traditional process
management approach in the healthcare context; it has developed a process-aware system where the emphasis relies
on assisting the clinicians through the availability of recommended healthcare pathways, together with the provision of
relevant information (such as the impact of certain medications, contraindications, etc.) that reduce the risk arising from
a personal decision. Care pathways are presented in the form of “best practices” (or clinical “guidelines”) and provide
clinicians with appropriate knowledge to enact the medical treatments.
TESTMED aims, on one side, at finding an effective way for the clinicians to exploit the guidelines, i.e., to acquire, by
reading or listening, the guideline and to make effective use of it. We believe that the adoption of mobile devices with
specific user interfaces (which do not distract the clinician from assisting the patient) can be a valuable solution. We
have investigated the integration of voice and touch interfaces with interesting results that will be shown in the
following. On the other side, the TESTMED prototype is able to trace and monitor every choice originated during the
guideline execution. The TESTMED prototype has been jointly developed and evaluated with the Emergency Department
(DEA) of Policlinico Umberto I - the main hospital in Rome (Italy). The first tests have concerned the guideline enacted
1
The acronym TESTMED stands for “meTodiche e tEcniche per la gestione dei processi nella Medicina D'urgenza (in English,
methods and techniques for process management in emergency healthcare).
18
2
for patients suffering from chest pain . Leveraging the encouraging results of our initial tests, we plan to perform in the
next months an extensive system evaluation and validation. This will require the enactment of additional guidelines, as
well as the collection of both quantitative and qualitative data for assessing the real impact on clinical work practices.
Methods
The doctor in charge of handling an incoming patient is equipped with a tablet PC that enables the clinician to select,
instantiate and carry out the specific care pathway to be followed. According to a patient-centered clinical approach, the
care pathway is selected on a per-case basis from a dedicated repository and loaded into the back-end management
system to be executed.
Client components deployed on the tablet device provide support for both multitouch and speech-based interaction
modalities. In particular, the user interface relies on an integrated multitouch and speech recognition/generation
framework, able to handle both touch and vocal inputs, and to support device-to-human interaction via text-to-speech
capabilities. The interaction between client and back-end components is supported by communication and notification
services. According to a service-oriented approach, all system components are abstracted as service endpoints and
interact through message-based service invocations. In addition, event-based notification services provide support for
asynchronous communication patterns, required to enable the routing of events produced during the execution of a care
pathway. This allows the clinician to receive reminders, alerts and notifications when the status of an active process
changes, new information is available, or additional actions are required.
Similarly, all members of the medical staff (other clinicians, nurses, etc.) are equipped with mobile devices and are
notified of the progress of the care processes and of the different activities to be executed.
Care pathways are executed and managed by back-end system components, which provide the run-time environment
for interpreting, instantiating and activating a care pathway specification. The execution of clinical guidelines is
supported by properly routing data, events and activities, according to a process-aware and content-based approach
where activity scheduling and message dispatching are data/event-driven. Specifically, the interaction between all
involved components and services is managed by a routing engine that manages the routing of clinical activities,
relevant data and generated events among the different actors, services and information systems (fig. 1).
2
Chest pain is defined as a pain that ranges from the base of the nose and navel and between the neck and the twelfth vertebra
and that has no clearly identifiable traumatic cause, which is one of the most common reasons for the admission to the
emergency room (5% of all visits) with high mortality in case of misdiagnosis and improper dismissal (2--4%) [2].
19
Fig. 1 – Architecture
The routing engine relies on a scheduling component for the timely execution of activities with temporal constraints (eg.
examinations and diagnostic laboratory tests that have to be scheduled and performed within specific time intervals),
and interacts with the enterprise Electronic Medical Record (EMR) system to (i) access and retrieve clinical and
administrative patient data (fig. 2), (ii) schedule and manage examinations, lab tests, drug prescriptions, etc. according
to the clinical process (fig. 3), and (iii) receive events and notifications about test results and examination findings to be
routed and delivered to the clinicians (fig. 4).
20
Fig. 2 - Access and retrieve clinical and administrative patient data
21
Fig. 3 - Schedule and manage examinations
22
Fig. 4 - Receive events and notifications
The interoperability with the EMR system is achieved exploiting the Health Level 7. In this context, doctors and nurses
need to collaborate in order to enact the proper medical treatments for each patient. The use of mobile devices and
applications is valuable for the improvement of collaboration and coordination amongst clinicians, but there are also
risks in their usage; for example, most of the care activities could be highly critical and time demanding, and the
challenge concerns in developing a user interface that captures the users' attention onto the system only when it is
strictly required. The development of specific interaction principles has required the use of user-centered design (UCD)
23
techniques during the life cycle of the TESTMED project. Such methodologies rely on a continuous involvement of users
in each phase of the project, by guaranteeing that the final system may meet the user expectations.
Results
To be more specific, we produced two mockups of the system (in the months of April and September 2011) and a
working prototype in late November 2011. Each mockup/prototype has been evaluated throughout a wide range of
usability tests (controlled experiments, thinking aloud techniques, etc.) made with real clinicians, and the outcomes
have been used for an incremental improvement of the system. For example, despite users appreciated the touch
interface provided in the first mockup, they asked for an interaction with the system still less invasive. To match such a
request, the vocal interface (which can be used in addition to the touch interface) has been introduced in the second
mockup and definitively improved in the first working prototype. Concerning the current version of the TESTMED
prototype, we performed a test in the ward of DEA with 7 different users (specifically, 3 clinicians, 2 PhD student in
medicine and 3 experts in Information Technology) and with the Chest Pain procedure loaded into the system. We also
collected user opinions through a survey, and in general the feasibility of the twofold interaction and the idea to
coordinate medical treatments through a workflow engine have been accepted and deemed usable.
We would like to mention that, as a consequence of the introduction by the medical community of evidence-based
clinical guidelines to support decision processes, many research groups have focused on computer-interpretable clinical
guidelines (CIGs) and different languages have been proposed (3). All languages define a computer-interpretable
representation of clinical guidelines and most of them follow a task-based paradigm where modeling primitives for
representing actions, decisions and patient states are linked via scheduling and temporal constraints, often in a
flowchart-like structure. Many representation models are supported by systems that allow the definition and enactment
of clinical guideline. Supporting systems are based on distributed architectural models that include a guideline modeling
editor, a model repository and a run-time execution engine, as well as tools and services to access electronic medical
records (EMRs). Similarly, the introduction in healthcare of workflow-based models and technologies has fostered the
development of so-called Careflow Management Systems (CfMSs) that aim at providing an integrated solution for
supporting both administrative and medical processes. The NewGuide system (4), for example, relies on a Petri Nets
based formalism for modeling guidelines and implements a distributed architecture for integrating a Guideline
Management System (GlMS), an Electronic Patient Record (EPR) and a CfMS.
Discussion
We can argue that so far main research activities have focused on supporting guidelines modeling and process
management in static and well defined clinical contexts. Specific research activities have been carried out in the context
of emergency wards and first aid environments. According to reported results about the procedures, interaction patterns
and supporting systems, the main causes of delays, inefficiencies and medical errors can be ascribed to the lack of
proper interaction between the medical staff and the IT systems, which are, in turn, loosely integrated in healthcare
workflows, leading to duplicated or suboptimal task allocation policies. In emergency departments, which today
represent the main access point for citizens to healthcare services, the medical staff operates under stress conditions in
a rapidly evolving environment. Our work and initial effort can be broadly positioned in this context, where the
introduction of a process-aware system can lead to significant benefits for both patients and clinicians, allowing to
identify and analyze the sources of errors, delays and complexity (which may often go undetected) in order to improve
the overall performance.
Conclusion
In this paper we have presented the initial outcomes of the TESTMED project, aiming at studying and developing a
system supporting clinicians during their daily activities in hospital wards, through the interplay of advanced user
interfaces (i.e., mixing touch and vocal features) on mobile devices and the enactment and tracing of clinical guidelines.
The system prototype has been evaluated in clinical settings through the chest pain diagnostic and treatment process.
Preliminary evaluation results show a good degree of acceptance among medical staff members, and performance
results confirm the feasibility and potential applicability of multimodal interfaces. Starting from our initial results, the
rest of the project will be devoted to the engineering of the prototype and to an extensive validation process. By
providing support for additional guidelines, our evaluation plan includes the collection of quantitative and qualitative
24
indicators that in the long run will enable a deeper understanding of how the overall clinical decision making and
collaboration process is impacted.
References
1. Cossu F, Marrella A, Mecella M, et al. Improving operational support in hospital wards through vocal interfaces and
process-awareness. Computer-Based Medical Systems (CBMS), 25th International Symposium on, 2012.
2. Ottani F, Binetti N, Casagranda I, et al. Percorso di valutazione del dolore toracico -Valutazione dei requisiti di base
per l’implementazione negli ospedali italiani. Giornale Italiano di Cardiologia 2009; 10: 46–63.
3. de Clercq PA, Blom JA, Korsten HHM, Hasman A. Approaches for creating computer-interpretable guidelinesthat
facilitate decision support. Artificial Intelligence in Medicine 2004; 31(1): 1–27.
4. Ciccarese P, Caffi E, Boiocchi L, et al. A guideline management system. Studies in HealthTechnology and Informatics
2004; 107: 28–32.
Corresponding Author: Marianna Suppa
Emergency Medicine and Emergency Room, "Sapienza" University of Rome
Autore di riferimento: Marianna Suppa
Medicina d’Urgenza e Pronto Soccorso, “Sapienza” Università di Roma
25
Pathophysiology of acute postoperative pain and
scientific rationale of "pre-emptive analgesia”
PATHOPHYSIOLOGY OF ACUTE POSTOPERATIVE PAIN AND
SCIENTIFIC RATIONALE OF "PRE-EMPTIVE ANALGESIA”
FISIOPATOLOGIA DEL DOLORE ACUTO POST-OPERATORIO E RAZIONALE
SCIENTIFICO DELLA “PRE-EMPTIVE ANALGESIA”
FISIOPATOLOGÍA DEL DOLOR POSTOPERATORIO AGUDO Y FUNDAMENTO
CIENTÍFICO DE “PRE-EMPTIVE ANALGESIA”
De Angelis C1, Compare R1
1
1
1
DDS, Private practitioner, Rome, Italy
Odontoiatra, Libero professionista, Roma, Italia
Dentista, Roma, Italia
Citation: De Angelis C, Compare R. Pathophysiology of acute postoperative pain and scientific rationale of "pre-emptive
analgesia”. Prevent Res 2013; 3 (1): 26-33. Available from: http://www.preventionandresearch.com/ .
Key words: Pre-Emptive Analgesia, third molar surgery, Acute Postoperative Pain
Parole chiave: Pre-Emptive Analgesia, estrazione terzo molare incluso, Dolore Acuto Post-Operatorio
Descriptores: Analgesia preventiva, extracción de terceros molares incluidos, Dolor Agudo Postoperatorio
26
Abstract
Background: The dentoalveolar surgery, in particular the extraction of mandibular impacted third molars, is the most
commonly performed one in Oro-Maxillo-Facial surgery. As demonstrated by clinical experience, this type of intervention
can be affected by a series of post-operative sequelae, and Acute Postoperative Pain (APP) is the less tolerated one by
the patient. In recent decades, the practical need to minimize the pain that follow an extraction, together with improved
understanding of the pathophysiological mechanisms of pain, led to the research of new analgesic techniques. An
improvement was the idea to "prevent the pain development rather than treating it post-operatively", this innovation led
us to develop the technique known as "Pre-Emptive Analgesia" (preventive analgesia). Despite the promising results
obtained with “Pre-Emptive Analgesia” experimental models, clinical results are not unambiguous.
Objectives: The objective of this study is to describe the rational basis of “Pre-Emptive Analgesia” technique and its
controversies presented in literature concerning this analgesic method.
Methods: The method consisted in a careful analysis of the pathophysiological mechanisms underlying the acute postoperative pain in order to explain the scientific rationale of “Pre-Emptive Analgesia”.
Results: Despite the “Pre-Emptive Analgesia” has been amply demonstrated in experimental models, its practical
application is still very much debated. The conflict subjects are the proper name and the definition of “Pre-Emptive
Analgesia”, as well as the drug choice that is used for the pre-emptive treatment and its treatment regimen (route of
administration, timing, dose, dosage and duration of treatment). Another problem concerning the “Pre-Emptive
Analgesia” is that the most of clinical studies concern major surgery in which painful stimuli differ widely in terms of
intensity and duration to those obtained in ambulatory surgery with local anaesthetics. It is also demonstrated that “PreEmptive Analgesia” effectiveness is influenced by the type of surgery performed. Moreover, considering the fact that the
acute post-operative pain, being a multidimensional experience, is linked to psychological factors that influence the
results obtained with the “Pre-Emptive Analgesia”.
Discussion and Conclusions: The concept of "Pre-Emptive Analgesia" evolved in the course of time until it was
definitively given the correct rational basis on which it is based, but unfortunately it still remains a very controversial
topic. Despite that, the clinicians’ confidence about the potential of pre-emptive analgesia remains high. It is therefore
clear that further studies are needed to arrive at an unanimous opinion in the scientific community regarding its clinical
application in ambulatory oral surgery.
Abstract
Introduzione: La chirurgia dentoalveolare, in particolare l’estrazione dei terzi molari mandibolari inclusi, è l’intervento
più comunemente eseguito nel campo della Chirurgia Oro-Maxillo-Facciale. Come dimostrato dall’esperienza clinica,
questo tipo di intervento può essere gravato da una serie di sequele post-operatorie, di cui la meno tollerata dal
paziente è il Dolore Acuto Post-Operatorio (Acute Postoperative Pain, APP). Negli ultimi decenni, la necessità pratica di
minimizzare il sintomo doloroso post-avulsivo, assieme alla migliorata comprensione dei meccanismi fisiopatologici del
dolore, hanno portato alla ricerca di nuove tecniche analgesiche. Una svolta si è avuta con l’introduzione dell’idea di
“prevenire lo sviluppo del dolore anziché trattarlo post-operatoriamente”, innovazione che ha portato a sviluppare la
tecnica nota come “Pre-Emptive Analgesia” (analgesia preventiva). Nonostante i promettenti risultati ottenuti dalla PreEmptive Analgesia nei modelli sperimentali, i risultati clinici non sono altrettanto univoci.
Obiettivi: Il presente articolo si pone lo scopo di descrivere quello che è il razionale di base di questa tecnica e le
controversie presenti in letteratura relativamente a questa metodica analgesica.
27
Metodi: I metodi sono consistiti in un’accurata analisi dei meccanismi fisiopatologici alla base del dolore acuto postoperatorio , allo scopo di spiegare il razionale scientifico della “Pre-Emptive Analgesia”.
Risultati: Nonostante la “Pre-Emptive Analgesia” sia stata ampiamente dimostrata nel modello sperimentale, la sua
applicazione pratica è ancora profondamente dibattuta. I motivi di contrasto spaziano dalla corretta denominazione e
definizione della “Pre-Emptive Analgesia”, fino alla scelta del farmaco da usare per il trattamento Pre-Emptive ed il suo
regime di utilizzo (via di somministrazione, timing, dose, posologia e durata del trattamento). Un altro problema
inerente la “Pre-Emptive Analgesia” riguarda il fatto che la maggior parte degli studi clinici si riferiscono ad interventi di
chirurgia maggiore, in cui gli stimoli dolorosi differiscono molto per natura intensità e durata da quelli ottenuti in
chirurgia ambulatoriale e anestesia locale. Inoltre è appurato che l’efficacia della “Pre-Emptive Analgesia” è influenzata
dal tipo di chirurgia eseguita. Occorre infine considerare il fatto che il Dolore Acuto Post-Operatorio, essendo
un’esperienza multidimensionale, è legata a fattori di carattere psicologico che influenzano i risultati ottenibili con la
“Pre-Emptive Analgesia”.
Discussione e Conclusioni: Il concetto di “Pre-Emptive Analgesia” si è evoluto nel corso del tempo fino ad arrivare a
determinare in maniera definitiva il corretto razionale di base su cui si fonda, anche se rimane ancora oggi un
argomento molto controverso. Nonostante questo, la fiducia dei clinici circa le potenzialità della “Pre-Emptive Analgesia”
rimane alta. Appare quindi evidente la necessità di ulteriori studi per giungere ad un’opinione concorde nella comunità
scientifica internazionale riguardo alla sua applicazione clinica in chirurgia orale ambulatoriale.
Resumen
Introducción: La Cirugía dentoalveolar, en particular la extracción de terceros molares mandibulares incluidos, es la
cirugía más comúnmente realizada en Oro-maxilofacial. Como la experiencia clínica demuestra, este tipo de intervención
puede ser cargado por una serie de secuelas postoperatorias; la menos tolerada por el paciente es el Dolor Agudo PostOperatorio (Acute Postoperative Pain, APP). En las últimas décadas, la necesidad práctica para reducir al mínimo los
síntomos de dolor post-avulsivo y para mejorar la comprensión de los mecanismos fisiopatológicos del dolor, han llevado
a la búsqueda de nuevas técnicas analgésicas. Un avance se produjo con la introducción de la idea de "prevenir el
desarrollo del dolor" en lugar de tratarlo Post-Operatorialmente; esta innovación ha llevado a desarrollar la técnica
conocida como “Pre-Emptive Analgesia” (analgesia preventiva).
A pesar de los prometedores resultados de la "Pre-Emptive Analgesia” en modelos experimentales, los resultados
clínicos no son igualmente únicos.
Objetivos: Este artículo pretende describir lo que es la base racional de esta técnica y las controversias en literatura
sobre esta metódica analgesica.
Métodos: Los métodos consistieron en un análisis profundo de los mecanismos fisiopatológicos a la base del dolor
agudo postoperatorio para explicar el fundamento científico de la “analgesia preventiva”.
Resultados: La aplicación práctica de la “analgesia preventiva” es aún muy discutida. Los motivos de contraste
concernen la denominación correcta de la “analgesia preventiva” y la elección del fármaco para el tratamiento
preventivo y su régimen de utilización (vía de administración, dosis, tiempo, dosis y duración del tratamiento). Otro
problema inherente a la “analgesia preventiva” es que la mayoría de los estudios clínicos se refieren a una cirugía mayor
en la que los estímulos dolorosos difieren por intensidad y duración de los obtenidos en cirugía ambulatoria y anestesia
local. Es aclarado que la eficacia de la “analgesia preventiva” está influenciada por el tipo de cirugía realizada. También
28
debe tenerse en cuenta el hecho de que el dolor postoperatorio, siendo una experiencia multidimensional, está vinculada
a factores psicológicos que influyen en los resultados que se pueden alcanzar con la “analgesia preventiva”.
Discusión y Conclusiones: El concepto de “Pre-Emptive Analgesia” se ha evolucionado con el tiempo hasta llegar a
determinar definitivamente el correcto racional de base en el que se funda, pero, sigue siendo un tema muy
controvertido. A pesar de esto, la confianza de los médicos sobre el potencial de la “analgesia preventiva” sigue siendo
alta. Por lo tanto, es clara la necesidad de más estudios para llegar a una concorde opinión en la comunidad científica
internacional sobre su aplicación clínica en la cirugía oral ambulatoria.
Background
Dentoalveolar surgery, in particular the surgical extraction of mandibular third molars, is the procedure most commonly
performed in Oro-Maxillo-Facial Surgery (1) and it is also the most affected one by a series of post-operative squeals, of
which the main are trismus (2), edema and Acute Postoperative Pain (3) (APP). Among these symptoms, pain is the less
tolerated one by patients and its inadequate treatment causes physical and psychological discomfort, and increases
morbidity with negative impact on life quality (4). In recent decades, as a result of improved understanding of the
pathophysiology of acute pain in both peripheral and central mechanisms, there has been a remarkable improvement in
the clinical management of APP, e.g. anticipating the treatment timing or preventing the pain onset rather than treating
it postoperatively. This revolutionary concept of "pain prevention", formulated for the first time by G. W. Crile at the
beginning of the last century, is now the basis of the so-called "Pre-Emptive Analgesia" technique (5) ("preventive
analgesia").
Objectives
This paper aims, through a detailed examination of the acute pain pathophysiology, to identify the rational basis of the
"Pre-Emptive Analgesia" and to describe the methodological controversies raised in the scientific community about its
clinical application.
Methods
Physiopathology of APP
Pain following surgical extraction of mandibular impacted third molars is a symptom that derives from the activation of a
local inflammatory response in peripheral tissues affected by surgical trauma (6), which leads to the release of a variety
of biochemical mediators and algogenic substances (the so-called "sensitizing soup") (7) by the free nerve endings
(nociceptors) and extraneural sources of traumatized tissues (muscles, ligaments, mucous, blood vessels and nerves).
For this reason, the Acute Post-Operative Pain is also called "inflammatory" or "nociceptive" pain.
From the clinical point of view, the increase of the release of inflammatory mediators appears to be related more to the
extraction trauma, especially against the bone tissue support, rather than to its duration. Moreover, the intensity of the
inflammatory mediators release is the basis of the physiological "curve of pain", i.e. the change in the post-operative
period of the pain level experienced. The Post-Operative Acute Pain in fact reaches a moderate/severe level within the
first 24 hours after the surgery and it reaches a peak at 3-5 or 6-8 hours after the extraction (8), and then if there are
not any inflammatory complications it tends to decrease gradually and it usually disappears or the intensity becomes
negligible after the second day (9).
The chemical mediators of inflammation, including potassium (K+), histamine (H), acetylcholine (ACh), serotonin (5-HT),
adenosine triphosphate (ATP), bradykinin (BK), leukotrienes (LT), substance P (SP) and prostaglandin (PG) (10, 11),
reach their maximum local tissue concentration during the first 48-72 hours after the surgery, causing vascular and
neuronal effects (12). The former are represented by the vasodilation and by increased vascular permeability, while the
latter consists in peripheral and central modification of neuronal activity (sensitization) (13) and are responsible for
developing the APP (14). It is important to highlight that post-traumatic peripheral pain signals are transmitted in two
phases, the first one occurs during the surgery, the second one during the healing of the surgical wound (7).
29
In the peripheral tissues, the overall action of inflammatory mediators determines the activation and sensitization of
nociceptors (free nerve endings or peripheral nerves) (15), inducing spontaneous activity and amplification of
responsiveness to stimuli (primary hyperalgesia), reduction of pain threshold (allodynia) and prolonged responses to
stimuli above-threshold for pain (hyperpathia) (7), leading to an altered transduction and an increased conduction of
pain impulses to the central nervous system (CNS). This magnification (6) of all nervous traffic and afferent algic stimuli
also extends to the tissues surrounding the traumatized area (secondary hyperalgesia).
At central level it occurs, however, an increase in activity-dependent excitability of Nociception-Specific Neurons (NS)
and of Wide Dynamic Range Neurons (WDR) of the spinal cord or the trigeminal nucleus (12) (being this nerve mainly
interested in oral surgery), so that:
1)
They become more susceptible and more responsive to afferent peripheral input, by favoring the phenomena of
both primary and secondary peripheral hyperalgesia and allodynia;
2)
They extend and amplify painful afferent inputs.
Pain signal transmission continues at a supraspinal level until it reaches the thalamus and other brain regions, where the
pain stimulus is finally converted into subjective and emotional feelings perceived by the subject. Usually, the peripheral
and central sensitizations occur together (12) and they both contribute to the state of painful post-traumatic
hypersensitivity.
In sum, the pain that is associated with tissue damage causes a prolonged modulation of the somatosensory system,
with an increased responsiveness of both central and peripheral pain pathways.
The "Pre-Emptive Analgesia" recognizes its rational basis in the prevention of molecules formation and their consequent
release that can cause hyperalgesia in traumatized tissues (16) and also in the prevention or minimization of the central
sensitization (11), which is inevitably linked to surgical trauma. In fact, the trauma prolongs and promotes the
peripheral sensitization status. Preventing or minimizing only the peripheral sensitization is inadequate, because as soon
as the sensitization of the CNS has been established, the APP persists in an abnormal state of activation and can be
stimulated also by subthreshold signals. The "Pre-Emptive Analgesia" try therefore to reduce the overall APP level felt by
the patient preventing the pain development
in all its phases, or intervening on the activation of the nociceptive
cascade due to surgical trauma (development of pain), blocking the arrival of the pain stimulus to the spinal cord (pain
amplification) and avoiding that the afferent barrier generated by the tissue injury reaches the central nervous system
until healing has occured (maintenance of pain) (7).
Results
Disputes over "Pre-Emptive Analgesia"
Despite it is well defined the scientific rationale, on which the "Pre-Emptive Analgesia" is based, in recent years its
application in clinical practice has been the subject of numerous methodological debates that led to confusion,
misunderstandings and disagreements in the international scientific community (17). Even now, a shared opinion is not
reached and the "Pre-Emptive Analgesia" definition and description continue to be subject matters for discussions. In
fact, considering the scientific rationale on which it is based the "pre-emptive analgesia" expression is nowadays
obsolete, because:
1)
it can be misunderstood, because the name of this technique should emphasize the pathophysiological
phenomenon that it allows to prevent (i.e. the onset of central sensitization) instead of the final effect that it allows
to obtain (prevention of pain);
2)
it is a limited expression, since the "Pre-Emptive Analgesia" should not be simply considered as a "pre-operative"
analgesia (18); but, considering its bi-phasic post-traumatic painful stimuli
nature, it should be continued in a
continuous and constant way (19, 20, 21) for the whole period in which the pain stimuli occur (pre-, intra-, postoperatively), so that a protective and preventive analgesia can be achieved (21, 22).
For these reasons, in order to try to eliminate the inherent limitations of the old name and to expand the concept of
"prevention of pain” many different alternative names have been proposed in literature (such as "Preventive Analgesia",
30
"Protective Analgesia", "Balanced Peri-Emptive Analgesia", "Pre-Emptive Antihyperalgesia") (17). Another issue, partly
caused by the lack of agreement on its definition and description, is the evidence for successful treatments of this
technique in animal experiments versus disappointing human clinical trial results. This difference is related to many
factors, mainly the difficult identification of the "primary nociceptive event", at the time that the pre-emptive treatment
should be already started. In fact, some authors restrict the painful stimuli as the onset of the surgical procedure while
others as the entire duration of the surgical procedure, and as a result, some clinical studies have compared identical or
very similar analgesic treatment started before versus after the first surgical incision, while others have compared the
administration of different analgesic regimens, with each other or with placebo (11).
In the animal model, then, the nociceptive stimulus does not affect highly differentiated tissues with complex
innervation, as opposed to clinical practice (23). Many reviews have also shown that clinical results, concerning "PreEmptive Analgesia", are influenced by different anatomical areas (degree and type of innervation), type of surgery (23)
(orthopedic, oral, gynecological, etc.) and type and duration of anesthesia performed.
The debate over the "Pre-Emptive Analgesia" concerns the choice of the pharmacological pre-emptive drug and its
dosage, timing, route of administration and treatment period (24). Although even now there is no agreement in
literature, current strategies pay particular attention to the use of drug combinations with different mechanisms of
action rather than a single analgesic agent. In addition, being local anesthetics equipped with pre-emptive effects (25),
in order to evaluate the effectiveness of the "Pre-Emptive Analgesia" in ambulatory oral surgery, it should always be
considered the possibility that the local anesthesia could mask the effect of the pre-emptive drug, explaining many
discrepant clinical trial results. Moreover, it should also be considered, the surgeon’s skills
[24]
. Another issue is whether
other aspects that contribute to the overall peri-operative pain, such as psychological factors related to the patient, are
sufficient in terms of intensity and duration to mask any benefits obtained by the pre-emptive treatment. In fact, despite
its typical nociceptive nature, the
constant pain level (ranging from moderate to severe), the pathophysiological
mechanisms of development similar to those of other types of acute pain, the ability to reproduce (in specular inclusion
cases) and to quantify it (VAS scales, NS, VRS, NRS) (26) and its “symptomatic” intrinsic nature
makes the APP a
subjective experience, and thus linked t psycho-affective factors that in the experimental model not necessarily exist
and do not influence the results.
Since its introduction in medical literature, the concept of "Pre-Emptive Analgesia" has undergone changes, until it was
reached a definitive correct rational basis. The main Pre-Emptive Analgesia features are (27):
1)
The analgesic treatment starts before the nociceptive primary event is caused;
2)
The preventive drug treatment is maintained throughout the perioperative period;
3)
The onset of the central sensitization state, caused by the nociceptive primary event is prevented;
4)
The central sensitization caused by peripheral inflammatory response is prevented.
To date, there are still many controversial points about the clinical application of the "Pre-Emptive Analgesia". In fact,
clinical trial results tend to be disappointing. Moreover, the most of clinical trials refer to major surgery (23), in which
painful stimuli differ greatly in intensity and duration from those of ambulatory surgery under local anesthesia. Another
confounding factor is the different type of surgery and method chosen for conducting the study.
However, even now the "Pre-Emptive Analgesia" seems to be the most appropriate treatment for APP (28), although,
considering the multidimensional nature of pain sensation, a good pain management should always be associated with
appropriate clinical and psychological care. As always, then, the principle that prevention is better than cure seems to be
valid.
31
Conflicts of interests
The authors declare that there are no conflicts of interest.
Funding to the study
The authors state that they received no institutional funding for this study.
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Ong Cliff KS, Seymour RA. An evidence-based update of the use of analgesics in dentistry. Periodontology 2000,
9.
Kaczmarzyk T, Wichlinski J, Stypulkowska J, et al. Preemptive effect of ketoprofen on postoperative pain following
perception after surgical removal of third molars. Journal of Oral and Maxillofacial Surgery 2009; 67(5):1083-1091.
the inflammatory response. Part 1 of 3 – A unifying law of pain. Medical Hypoteses 2007; 69(1):70-82.
2008; 46(1):143-164.
third molar surgery. A prospective, randomized, double-blinded clinical trial. International Journal of Oral and
Maxillofacial Surgery 2010; 39(7):647-652.
10.
Dray A. Inflammatory mediators of pain. Review. British Journal of Anaesthesia 1995; 75(2):125-131.
11.
Dahl JB, Møiniche S. Pre-emptive analgesia. British Medical Bulletin 2004; 71:13-27.
12.
Ong Cliff KS, Seymour RA. Pathogenesis of postoperative oral surgical pain. Anesthesia Progress 2003; 50(1):5-17.
13.
Yun Y. Mechanisms of postoperative pain. Chinese Medical Journal 2007; 120(22):1949-1950.
14.
Ochroch EA, Mardini IA, Gottschalk A. What is the role of NSAIDs in pre-emptive analgesia? Drugs 2003;
63(24):2709-2723.
15.
Schaible HG, Richter F. Pathophysiology of pain. Langenbeck’s Archives of Surgery 2004; 389(4):237-243.
16.
Ong Cliff KS, Seymour RA. An evidence-based update of the use of analgesics in dentistry. Periodontology 2000,
2008; 46(1):143-164.
17.
Katz J, Clarke H, Seltzer Z. Preventive analgesia: quo vadimus? Anesthesia and Analgesia 2011; 113(5):1242-
18.
Kissin I. Preemptive analgesia at the crossroad. Anesthesia and Analgesia 2005; 100(3):754-756.
19.
Kissin I. Preemptive analgesia. Anesthesiology 2000; 93(4):1138-1143.
20.
Joshi A, Parara E, Macfarlane TV. A double-blind randomized controlled clinical trial of the effect of preoperative
1253.
ibuprofen, diclofenac, paracetamol with codeine and placebo tablets for relief of postoperative pain after removal of
impacted third molars. British Journal of Oral and Maxillofacial Surgery 2004; 42(4):299-306.
21.
Katz J, McCartney CJL. Current status of pre-emptive analgesia. Current Opinion in Anaesthesiology 2002;
15(4):435-441.
32
22.
Møiniche S, Kehlet H, Dahl JB. A qualitative and quantitative systematic review of preemptive analgesia for
23.
Aida S, Baba H, Yamakuka T, et al. The effectiveness of preemptive analgesia varies according to the type of
postoperative pain relief. Anesthesiology 2002; 96(3):725-741.
surgery: a randomized, double-blind study. Anesthesia and Analgesia 1999; 89(3):711-716.
24.
Campiglia L, Consales G, De Gaudio AR. Pre-emptive analgesia for postoperative pain control. A review. Clinical
Drug Investigation 2010; 30(Suppl. 2): 15-26.
25.
Jung YS, Kim MK, Um YS, et al. The effects on postoperative oral surgery pain by varying NSAID administration
times: comparison on effect of preemptive analgesia. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology &
Endodontics 2005; 100(5):559-563.
26.
Litkowski LJ, Christensen SE, Adamson DN, et al. Analgesic efficacy and tolerability of oxycodone 5 mg/ibuprofen
400 mg compared with those of oxycodone 5 mg/acetaminophen 325 mg and hydrocodone 7.5 mg/acetaminophen
500 mg in patients with moderate to severe postoperative pain: a randomized, double-blind, placebo-controlled,
single-dose, parallel-group study in a dental pain model. Clinical Therapeutics 2005; 27(4):418-429.
27.
Piecuch JF. What Strategies Are Helpful in the Operative Management of Third Molars? Journal of Oral and
Maxillofacial Surgery 2012; 70(Suppl. 1):25-32.
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Annibali S, De Biase A, Pippi R, Sfasciotti GL. A Consensus Conference on management of the lower third molar.
Minerva Stomatologica 2011; 60(10):509-527.
Corresponding Author: Chiara De Angelis
DDS, Private practitioner, Rome, Italy
Autore di riferimento: Chiara De Angelis
Odontoiatra, Libero professionista, Roma, Italia
Autor de Referencia: Chiara De Angelis
Dentista, Roma, Italia
33
In vitro percutaneous penetration of polycyclic aromatic
hydrocarbons from sunscreen creams
IN VITRO PERCUTANEOUS PENETRATION OF POLYCYCLIC
AROMATIC HYDROCARBONS FROM SUNSCREEN CREAMS
PENETRAZIONE PERCUTANEA IN
AROMATICI DALLE CREME SOLARI
VITRO
DI
IDROCARBURI
POLICICLICI
Paolucci V 1, Liberatori R1, Pescaglini M1, Sartorelli P1
1
Unit of Occupational Medicine, Department of Medical Surgical and Neurological Sciences,
University of Siena, Italy
1
UO Medicina del Lavoro, Dipartimento di Scienze Mediche Chirurgiche e Neuroscienze,
Università degli Studi di Siena
Citation: Paolucci V, Liberatori R, Pescaglini M, Sartorelli P. In vitro percutaneous penetration of polycyclic aromatic
hydrocarbons from sunscreen creams. Prevent Res 2013; 3 (1):34-38.
Available from: http://www.preventionandresearch.com/ .
Key words: Polycyclic Aromatic Hydrocarbons, sunscreen creams, percutaneous penetration
Parole chiave: Idrocarburi Policiclici Aromatici, creme solari, assorbimento prercutaneo
Abstract
Background: Dermal exposure to Polycyclic Aromatic Hydrocarbons (PAHs) affects many outdoor workers such as
asphalt workers. Usually the use of sunscreen creams is suggested to protect them from UV radiation. However
sunscreen could prevent or facilitate dermal absorption of industrial chemicals.
34
Objectives: The aim of the study was to assess percutaneous penetration of anthracene using 2 different sunscreen
creams as vehicle.
Methods: In vitro permeation experiments were carried out using standardized in vitro methods with static diffusion
cells. Excised human skin prepared to approximately 350 m thickness was fixed on the diffusion cells. The receiving
phase was a saline solution with 6% PEG 20. The 2 sunscreen creams (one lipophilic and one idrophilic) were applied
uniformly (2mg/cm2) on the skin mounted on the diffusion cell. After 20 minutes a solution of anthracene and artificial
sweat was added. Analysis of anthracene in the receptor samples was carried out by beta counter analyzer (Packard).
Results: Results did not show a percutaneous penetration of anthracene from sunscreen creams while in previous
studies in vitro percutaneous penetration of anthracene was demonstrated using the same methodology.
Discussion and Conclusion: The use of sunscreen creams among outdoor workers, would not seem to enhance
percutaneous penetration of PAHs. On the contrary it would be able to reduce dermal absorption of anthracene in the
workplace.
Abstract
Introduzione: L’esposizione cutanea ad Idrocarburi Policiclici Aromatici (IPA) interessa molti lavoratori outdoor quali gli
asfaltatori. Generalmente si suggerisce di proteggerli dalle radiazione UV per mezzo di creme solari. Tuttavia tali creme
potrebbero facilitare la penetrazione di tossici occupazionali.
Obiettivi: Scopo dello studio era valutare la penetrazione percutanea dell’antracene utilizzando come veicolo due
differenti creme solari.
Metodi: Gli esperimenti di passaggio percutaneo sono stati condotti utilizzando metodi in vitro standardizzati con celle
di diffusione statiche. Campioni di cute umana di circa 350 m di spessore erano fissati sulle celle di diffusione. Il fluido
recettore era costituito da soluzione salina con l’aggiunta di PEG 20 al 6%. Le due creme solari (una lipofila ed una
idrofila) erano applicate uniformemente (2mg/cm2) sulla cute montata nelle celle di diffusione. Dopo 20 minuti veniva
aggiunta una soluzione di antracene e sudore artificiale. L’analisi dell’antracene nei campioni di recettore era effettuata
mediante analizzatore beta counter (Packard).
Risultati: I risultati non mostravano un passaggio percutaneo di antracene dalle creme solari, mentre studi precedenti
avevano dimostrato la penetrazione transcutanea dell’antracene utilizzando la stessa metodologia.
Discussione e Conclusioni: L’impiego di creme solari nei lavoratori outdoor non sembra aumentare il passaggio
percutaneo degli IPA. Al contrario potrebbe ridurre l’assorbimento transcutaneo dell’antracene nei luoghi di lavoro.
35
Background
Polycyclic Aromatic Hydrocarbons (PAHs) are known to be absorbed through the skin (1, 2, 3). The contamination of
workers’ skin occurs in a variety of workplaces by deposition of vapors and particles or by splashing representing an
important route of uptake. Dermal exposure to PAHs affects many outdoor workers such as asphalt workers. Usually the
use of sunscreen creams is suggested to protect them from UV radiation. However sunscreens could prevent or facilitate
dermal absorption of industrial chemicals.
The aim of the study was to assess percutaneous penetration of anthracene after the application of 2 different sunscreen
creams (one lipophilic and one idrophilic).
Methods
In vitro permeation experiments were carried out using standardized in vitro methods (4) with static diffusion cells (FDC
400, Crown Glass Co, NJ US). The test apparatus was kept at a constant temperature of 37°C so that the skin surface
temperature was 32°C. Static ambered cells with individual magnetic stirring and an exposure area of 1.77 cm2
(diameter 1.5 cm) were used. Excised human skin (obtained from plastic surgery) prepared to approximately 350 m
thickness was fixed on the diffusion cells. Skin samples were frozen at -80° and stored for a maximum of 6 months. The
receiving phase was a saline solution with 6% PEG-20 oleyl-ether. Lipophilic substances such as PAHs were previously
found to diffuse well with this receptor (5). Yang et al (1986) using this type of experimental setting reported a similar
percutaneous absorption of anthracene in vivo on the rat and in vitro through dermotomed rat skin with an in vitro
penetration of 20% of the applied dose after 24 hours (6). The lipophilic and idrophilic sunscreen creams were applied
uniformly (2mg/cm2) on the skin mounted on 24 and 32 diffusion cells respectively. After 20 minutes a solution of [14C]labeled anthracene (Sigma Aldrich) and artificial sweat was added. Nine 500 µl samples for each cell were drown every
hour for 8 h and at 24 hours and replaced with receptor fluid. Analysis of
14
C-anthracene in the receptor samples was
carried out by beta counter analyzer (Packard).
Results
Results did not show a percutaneous penetration of anthracene after the application of sunscreen creams.
Conclusions
The use of sunscreen creams among outdoor workers would not seem to enhance percutaneous penetration of
anthracene. Taking into consideration the results there is no basis for considering that sunscreens facilitate dermal
absorption of PAHs.
Table 1 - In vitro percutaneous penetration through human skin of
63
Ni chloride e
57
Co chloride from two different
vehicles (14).
compound
vehicle
% after 24 h
(M ± SD)
%
in
the
% in the stratum
epidermis
corneum
(M ± SD)
(M ± SD)
63
Ni
water
0.23 ± 0.34
0.42 ± 0.55
50.33 ± 19.91
63
Ni
artificial sweat
0.76 ± 1.21
0.34 ± 0.19
36.16 ± 9.30
57
Co
water
1.04 ± 0.64
0.37 ± 0.20
27.62 ± 14.96
57
Co
artificial sweat
3.30 ± 2.65
0.23 ± 0.14
41.30 ± 18.83
36
Fig. 1 - In vitro cumulative percutaneous penetration through human skin of 203HgCl2 applied in two different
concentrations in an acqueous vehicle (13).
0 ,0 1 2
0 ,0 6 0 7 n m o l/c m 3
0 ,0 1
0 ,0 0 8 8 n m o l/c m 3
0 ,0 0 8
nmol/cm
2
0 ,0 0 6
0 ,0 0 4
0 ,0 0 2
0
1
2
8
16
24
32
40
48
56
64
72
tim e (h o u rs )
Fig. 2 - In vitro percutaneous penetration through human skin of 203HgCl2 applied in two different concentrations in
an acqueous vehicle (13).
6
5
0 ,0 6 0 7 n m o l/c m 3
0 ,0 0 8 8 n m o l/c m 3
percent dose
4
3
2
1
0
1
2
8
16
24
32
40
48
56
64
72
tim e (h o u rs)
37
References
1. Van Rooij JGM, Van Lieshout EMA, Bodelier-Bade MM, Jongeneelen FJ. Effect of the reduction of skin contamination
on the internal dose of creosote workers exposed to polycyclic aromatic hydrocarbons. Scand J Work Environ Health
1993; 19: 200-207.
2. Moody RP, Nadeau B, Chu I. In vivo and in vitro dermal absorption of benzo(a)pyrene in rat, guinea pig, human and
tissue-cultured skin. J Dermatol Sci 1995; 9: 48-58.
3. Fustinoni S, Campo L, Cirla PE, et al. Dermal exposure to polycyclic aromatic hydrocarbons in asphalt workers.
Occup Environ Med 2010; 67: 456-463.
4. Van de Sandt JJM, Van Burgsteden JA, et al. In vitro predictions of skin absorption of caffeine, testosterone and
benzoic acid: a multi-centre coparison study. Regul Toxicol Pharmacol 2004; 39: 271-281.
5. Bronaugh RL, Stewart RF. Methods for in vitro percutaneous absorption studies III: Hydrophobic compounds J Pharm
3. Sci 1984; 73: 1255-1258.
6. Yang JJ, Roy TA, Mackerer CR. Percutaneous absorption of anthracene in the rat: comparison of in vitro and in vitro.
Toxicol Ind Health 1986; 2: 79-84.
Corresponding Author: Pietro Sartorelli
Unit of Occupational Medicine, Department of Medical Surgical and Neurological Sciences,
University of Siena, Italy
Autore di riferimento: Pietro Sartorelli
UO Medicina del Lavoro, Dipartimento di Scienze Mediche Chirurgiche e Neuroscienze,
Università degli Studi di Siena
38
Chronic cerebro spinal venous insufficiency (CCSVI):
a new hypothesis for Multiple Sclerosis
CHRONIC CEREBRO SPINAL VENOUS INSUFFICIENCY
(CCSVI): A NEW HYPOTHESIS FOR MULTIPLE SCLEROSIS
L’INSUFFICIENZA VENOSA CRONICA CEREBRO SPINALE (CCSVI): UNA NUOVA
IPOTESI PER LA SCLEROSI MULTIPLA
Mandolesi S1, De Sio S2, Di Pastena C2, Scala B2, Loreti B2, Corbosiero P2, Sinibaldi F2, Sacco C2,
Mascia I2, Cappelli L2, Casale T2, Mandolesi D2
1
Department of Cardiovascular Sciences, Respiratory, and Geriatric Nephrology,
“Sapienza” University of Rome, Italy
2
Department of Anatomy, Histology, Medical-Legal and Orthopaedics, Unit of Occupational Medicine,
“Sapienza" University of Rome, Italy
1
2
Dipartimento di Scienze Cardiovascolari e Respiratorie, “Sapienza” Università di Roma
Dipartimento di Anatomia, Istologia, Medicina Legale e Ortopedia, Unità di Medicina del Lavoro,
“Sapienza” Università di Roma
Citation: Mandolesi S, De Sio S, Di Pastena, et al. Chronic cerebro spinal venous insufficiency (CCSVI):
a new hypothesis for Multiple Sclerosis. Prevent Res 2013; 3 (1): 39-44.
Key words: chronic cerebro-spinal venous insufficiency, Multiple Sclerosis,
venous compression, Zamboni
Parole chiave: Insufficienza venosa cronica cerebro spinale, Sclerosi Multipla,
compressione venosa, Zamboni
39
Abstract
A controversial nosologic vascular pattern recently identified by Prof. Paolo Zamboni of Ferrara and called Chronic
Cerebro Spinal Venous Insufficiency (CCSVI) was associated with multiple sclerosis, bringing a new diagnostics vision
and treatment of a disease which currently affects 70,000 Italians.
CCSVI is an hemodynamic condition, identified for the first time in 2009 by Prof Zamboni, in which there is an abnormal
venous drainage of cerebro-spinal fluid. The venous system obstacle through the internal jugular vein, vertebral veins
and the azygos system determines cerebro-spinal fluid stasis, venous reflux and flow reverse through a vicarious
cerebro-spinal circuit, resulting in a prolongation of the cerebral circulation, verified with diffusion magnetic resonance
studies. There are several clinical conditions such as abnormal coagulation, inflammation, neoplastic compression, which
can lead an acute obstruction of the cerebrospinal venous system resulting in severe clinical manifestations, such as
dizziness, stiff neck, headache, lethargy; in these conditions percutaneous angioplasty and loco-regional thrombolysis
treatments causes regression of symptoms. Zamboni has treated individuals suffering from Multiple Sclerosis’s CCSVI
with jugular and azygos angioplasty having positive results.
Abstract
Un controverso modello nosologico vascolare recentemente identificato dal Prof. Paolo Zamboni di Ferrara e definito
Insufficienza Venosa Cronica Cerebro Spinale (CCSVI) è stato associato alla Sclerosi Multipla portando una nuova visione
diagnostica e terapeutica di una malattia che ad oggi colpisce circa 70.000 Italiani.
La (CCSVI) è una condizione emodinamica, identificata e stigmatizzata nel 2009 dal Prof. Zamboni per la prima volta,
per la quale si ha un alterato drenaggio venoso cerebro-spinale; l’ostacolo al deflusso venoso attraverso il sistema della
vena giugulare interna, le vene vertebrali e il sistema dell’azygos determina stasi liquorale, reflusso venoso e inversione
del flusso cerebro-spinale attraverso un circuito vicariante, determinando un prolungamento del tempo di circolo
cerebrale, verificato con studi di diffusione con Risonanza Magnetica (RM). Esistono diverse condizioni cliniche, come
anomalie della coagulazione, infiammazioni, compressioni neoplastiche, che possono determinare un’ostruzione acuta
del sistema venoso cerebro-spinale con conseguenti gravi manifestazioni cliniche, quali confusione mentale, rigidità
nucale, cefalea, letargia; nelle suddette condizioni il trattamento percutaneo mediante angioplastica e trombolisi locoregionale determina regressione della sintomatologia. Su queste premesse Zamboni ha operato i primi soggetti con
Sclerosi Multipla affetti da CCSVI mediante angioplastica delle giugulari e Azygos con positivi risultati.
40
Description
The multiple sclerosis (MS) is an inflammatory-demyelinating disease of the brain and the spinal cord with multiple
neurological manifestations, above all in young adults (1).
The formation mechanism of the disease involves several steps: inflammation, demyelination and neuro-degeneration of
the central nervous system (1, 2, 3).
Charcot (4) established a possible link between venous vascular disorders and the inflammatory lesions characteristic of
multiple sclerosis, and after him, many researchers have noted the involvement of the venous structures in the
pathogenesis of plaque.
Recent studies show that most of the patients with multiple sclerosis are affected by chronic cerebro-spinal venous
insufficiency CCSVI (5, 6, 7, 8, 9).
As observed in several neurodegenerative diseases, the brain and the spinal cord of patients with MS contain high levels
of redox-active metals, especially iron (10), documented by MRI (11,12) and with histochemical methods (13, 14).
The way it reveals
MS is commonly divided into different clinical types (1, 2, 15):
RRMS: relapsing remitting multiple sclerosis (85%) (16);
SPMS: secondary progressive multiple sclerosis (15%) (15, 16);
SMPP: primary progressive multiple sclerosis (5%) (17).
RRMS is the most common type. Patients affected by this form tend to suffer from an attack or series of attacks
(relapses) followed by complete or partial remission (16). SPMS begins with relapsing-remitting MS (RRMS). It 's chronic
and progressive. There aren’t real periods of remission (15, 16).
PPMS is characterized by a gradual decline without clinical distinct periods, real or remission. The course of the disease
is a steady decline since the beginning (17).
The way it is diagnosed
The most commonly used tools in the diagnosis are (1, 2, 18, 19, 20):
• neuroimaging with magnetic resonance imaging (MRI) of the brain and the spine, which shows areas of demyelination
(lesions or plaques) with gadolinium (21, 22).
• Test of cerebrospinal fluid by a lumbar puncture, which can provide evidence of chronic inflammation of the central
nervous system for oligoclonal bands of IgG (23).
• The evoked potential by the stimulation of the optic nerve and sensory nerves, caused by demyelination. These brain
responses can be examined using visual and sensory evoked potentials (24).
Magnetic resonance venography (MRV) (7, 25) and post-mortem studies (26) show a correspondence between
topographic plaques of multiple sclerosis and cerebral venous system.
News in research
Recently, Prof. Zamboni (27) has raised the possibility that the chronic cerebro-spinal venous insufficiency could play a
decisive role in the genesis of the disease: he assumes that the obstructed venous outflow causes a redistribution of the
flow through the vicarious side insufficient to ensure an adequate flow resulting in stasis of red blood cells and T
lymphocytes at the level of endothelial junctions resulting in diapedesis of cells at the level of the brain tissue with
consequent accumulation of the same and hemosiderosis and inflammation.
Another important consideration in the genesis of vascular sclerosis is represented by the constant observation in MRI
examinations that the basic lesion is constituted by a ectasic vein at the center, surrounded by a plaque, which shows a
significant proportion of iron in its context (6, 7).
The microscopic analysis shows that the basal membrane of these deep veins is thickened with the constant presence of
hemosiderin intraparietal and in the surrounding territory; this alteration of the wall would be the basis of the damage of
the blood-brain barrier with a consequent infiltration of T lymphocytes and macrophages, which represents the trigger
autoimmune cascade mechanism that leads to the final result of demyelination and neurologic manifestations associated
with the multiple sclerosis (8, 9).
41
Prof. Zamboni (28, 29) reported the results of the study on 65 MS patients and 235 healthy controls of similar age. All
patients underwent transcranial and extracranial EcoColorDoppler (ECD)with the detection of at least two venous
alterations of the following five criteria revealing CCSVI:
Criterion 1: Reflux in the internal jugular vein and / or vertebral vein in the upright and supine;
Criterion 2: Reflux in the deep cerebral venous system;
Criterion 3: Evidence of stenosis of the jugular veins in the ECD;
Criterion 4: Not perceptible ECD flow in the lumen of the jugular and vertebral veins
Criterion 5: negative difference of the cross-section of the internal jugular in supine and standing positions.
The results of that study showed a correlation between Multiple Sclerosis and venous dysfunction in approximately
100% of subjects. Multiple and severe stenosis of the main load cerebrospinal venous segments were observed in the
patients, while the control group didn’t show any anomaly.
The 65 patients underwent selective venography of the jugular and of the azygos that confirmed in all patients the
symptoms described in ECD. The study confirmed the correlation between MS and CCSVI, but didn’t explain whether
CCSV followed MS or was the causes of it. Other studies (26, 29, 30, 31, 32), found a lower percentage (65%) of MS
patients with venous vascular anomalies for example Buffalo. In other studies comparing ECD and phlebography, the
percentage of MS patients with CCSVI is between 46% and 70% of those between 86% and 91% show signs of venous
steno-obstructive pulmonary disease (14, 15, 16).
Due to these observations the hypothesis that the treatment with vein plastic of the stenosis of the jugular and azygos
districts could lead to an improvement of the clinical situation was advanced (1, 2, 4, 17, 18, 19, 20).
Actually , in different situation and, sometimes with little scientific rigor, but encouraging results many experiences,
gave rise to a widespread use of angioplasty of the venous district.
Future prospects
The Department of Cardiovascular, Respiratory, and Geriatric Nephrology of Sapienza Policlinico Umberto I since
October-November 2010 has set up a Centre of Excellence for CCSVI and the National Epidemiologic center CCSVI
located in the Institute of Cardiology directed by Prof. Francesco Fedele.
After a short starting period a study protocol and treatment of CCSVI began in collaboration with the service of
Interventional Radiology department of the S. Andrea University Hospital. The "Sapienza CCSVI Centre " was the first in
Italy to perform ECD and to show the results on a Hemodynamics and Morphologic map (31) which allowed, a specific
algorithm to identify three types of CCSVI:
Type1 with endovascular blocks,
Type2 with blocks of the venous drainage from compression of the vessels,
Type3 with both endovascular block and extravascular compression.
The first statistical analysis of over 500 cases with multiple sclerosis studied with intra-and extracranial venous ECD in
our "Sapienza" CCSVI Centre found the presence of CCSVI according to the criteria identified by Zamboni in 83% of
cases.
Conclusions
After the positive preliminary results we believe a comprehensive epidemiological diagnostic and therapeutic study is
necessary for a better understanding of this new nosological entity that may open a new therapeutic hope for the people
suffering from MS.
42
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Ist Super Sanita 2005;41:143–164.
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ambulatory impairment in multiple sclerosis. J Neurol Sci 2005;234:17–24.
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Super Sanita 2005;41:143–164.
14. LeVine SM, Chakrabarty A. The role of iron in the pathogenesis of experimental allergic encephalomyelitis and
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Subcommittee of the American Academy of Neurology. Neurology 2000;54(9):1720–1725.
25. Hojnacki D, Zamboni P, Lopez-Soriano A, et al. Use of neck magnetic resonance venography, Doppler sonography
and selective venography for diagnosis of chronic cerebrospinal venous insufficiency: a pilot study in multiple
sclerosis patients and healthy controls. Int Angiol 2010;29(2):127-139.
26. Jeroen JG, Geurts, Lars Bo¨, at al. Cortical Lesions in Multiple Sclerosis: Combined Postmortem MR Imaging and
Histopathology. AJNR Am J Neuroradiol 2005;26:572–577.
43
27. Zamboni P, Galeotti R, Menegatti E, et al. Chronic cerebrospinal venous insufficiency in patients with multiple
sclerosis. J Neurol Neurosurg Psychiatry 2009;80:392-399.
28. Zamboni P, Menegatti E. Doppler Haemodynamics of Cerebral Venous Return.
Current Neurovascular Research 2008;5(4):260-265.
29. Zamboni P, Menegatti E, Galeotti R, et al. The value of cerebral Doppler venous hemodynamics in the assessment of
multiple sclerosis. J Neurol Sci 2009;282:21-27.
30. Zamboni P, Menegatti E, Bartolomei I, et al. Intracranial venous hemodynamics in multiple sclerosis.
Curr Neurovasc Res 2007;4:252-258.
31. Franceschi C. The unsolved puzzle of multiple sclerosis and venous function.
J Neurol Neurosurg Psychiatry 2009;80: 358.
32. Mandolesi S. L'attivazione Doppler del circolo venoso superficiale degli arti inferiori (metodiche di studio). Minerva
Angiol 1992;17(2 Suppl.3):159.
Corresponding Author: Sandro Mandolesi
Department of Cardiovascular Sciences, Respiratory, and Geriatric Nephrology,
“Sapienza” University of Rome, Italy
Autore di riferimento: Sandro Mandolesi
Dipartimento di Scienze Cardiovascolari e Respiratorie, “Sapienza” Università di Roma
44
Enterobius vermicularis: endoscopic opportunistic
diagnosis in a poorly symptomatic infection
ENTEROBIUS VERMICULARIS: ENDOSCOPIC OPPORTUNISTIC
DIAGNOSIS IN A POORLY SYMPTOMATIC INFECTION.
ENTEROBIUS VERMICULARIS: UNA DIAGNOSI ENDOSCOPICA OCCASIONALE IN
UNA OSSIURIASI PAUCISINTOMATICA.
Pontone S1, Leonetti G1, Brighi M1, Pontone P1
1
1
Citation: Pontone S, Leonetti G, Brighi M, Pontone P. Enterobius vermicularis: endoscopic opportunistic diagnosis in a
poorly symptomatic infection. Prevent Res 2013; 3 (1):45-49.
Key words: Enterobius vermicularis, Oxyuriasis, Parasitic infection, Colonoscopy
Parole chiave: Enterobius vermicularis, Ossiuriasi, Infezioni parassitarie, Colonscopia
Abstract
Enterobius vermicularis gastrointestinal infestation is considered as the most common helminthes infection worldwide
and is promoted by inadequate personal and community hygiene. The parasite have a hand-to-mouth transmission
resulting from scratching of perianal region, where the female parasite lays its eggs. Usually there are few symptoms as
the infection is well tolerate. More frequently in children this infestation may be responsible for several non-specific (loss
of appetite, abdominal pain, irritability, and pallor) and peculiar symptoms (anal itching, sleep disorders, restlessness
and irritability). Scratching often cause skin irritation that, in more severe cases, arise through eczematous dermatitis,
haemorrhage or secondary bacterial infections. Sometimes the infection can reach the female genital tract causing pelvic
manifestations. When oxyuriasis is suspected, the confirmation is obtained by cello-tape test and the mebendazole based
45
treatment is usually effective. Coproscopic tests may establish the diagnosis also in unclear cases without typical
symptoms. Treatment includes an antihelminthic agent for the patient and household members as well as home hygiene
measures. The diagnosis in adult patients is infrequent as the appearance of specimens during colonoscopy and
endoscopists may not suspect its presence. However, the association of Enterobius vermicularis infestation with acute
appendicitis varies from 0.2–41.8%. Thus, the early differential diagnosis, in these cases can exclude surgery and postoperative complications caused by the abdominal cavity parasitic contamination. We report about an endoscopic
diagnosis of oxyuriasis in a poorly symptomatic patient undergone colonoscopy as polypectomy follow-up.
Abstract
L’infezione intestinale da Enterobius vermicularis è considerata essere una delle più diffuse elmintiasi ed è
frequentemente associata ad una inadeguata igiene personale e di comunità. Questo parassita si trasmette per via orofecale infestando la regione perianale ove gli esemplari femminili adulti depositano le uova. Tipicamente l’infezione viene
ben tollerata vista la scarsità dei sintomi provocati. Più frequentemente nei bambini il parassita può essere responsabile
di sintomi aspecifici (anoressia, dolore addominale, irritabilità e pallore) e specifici (prurito anale, disturbi del sonno). Le
lesioni da grattamento, provocando una irritazione cutanea costante, nei casi più severi portano alla comparsa di
dermatite eczematosa, emorragia e superinfezione batterica. Talvolta l’infestazione può raggiungere il tratto genitourinario femminile causando manifestazioni pelviche. Qualora l’enterobiasi venga sospettata, lo Scotch Test rappresenta
un metodo mininvasivo per la conferma diagnostica, anche nei casi senza manifestazioni tipiche, ed il trattamento
mediante Mebendazolo una cura efficace. La diagnosi endoscopica, così come il sospetto diagnostico nell’adulto non è
frequente, così l’endoscopista potrebbe sotto pesare la possibile infestazione. Tuttavia, l’associazione tra enterobiasi ed
appendicite è dimostrabile nello 0.2-41.8% dei casi. Così, la diagnosi differenziale, in questi casi, se precocemente
effettuata, può escludere il trattamento chirurgico e conseguentemente le possibili complicanze postoperatorie ad esso
collegate. Nel nostro caso, viene descritto un caso di diagnosi esclusivamente endoscopica di ossiuriasi colica in un
paziente paucisintomatico, sottoposto a colonscopia totale per controllo in una pregressa polipectomia.
Background
Enterobius vermicularis (Ev) gastrointestinal infestation is considered as the most common helminthes infection (1) with
a high prevalence in developing countries (2). The fecal-oral route is the most common infection route for human. Poor
sanitation is closely linked to the dissemination of this parasite and young children are particularly at risk. More
frequently in children, the Ev infection may be responsible for loss of appetite, abdominal pain, irritability, and pallor,
but the most common symptom is sleep disturbance caused by pruritus ani (anal itching), reported in 33 percent of
patients (3). Thus, the parasite have a hand-to-mouth transmission resulting from scratching of perianal region, where
the female parasite lays its eggs (4). Usually there are few symptoms as the infection is well tolerate. However, rare
complications, primarily caused by the worms migrating into the genital and urinary tract, have been reported (5, 6, 7,
8, 9). When oxyuriasis is suspected, the confirmation is obtained by cello-tape test. This is an effective and minimally
invasive method that is performed in the morning pressing the tape onto the perianal area before bathing or defecation.
The microscope slide examination may reveal the eggs which are rarely found in the stool. The examination should be
repeated for three consecutive days to be effective. While in children the diagnosis is easy, sometimes in adults,
considering the embarrassment that may occur for this topic, the diagnosis is delayed (10). Furthermore, bowel
preparation (BP) prior to a colonoscopy examination frequently lowers the chances of detecting the worms
macroscopically (11). Thus, endoscopic diagnosis is infrequent as the endoscopist may not suspect its presence. In our
case, we describe a oxyuriasis in an apparently asymptomatic adult patient.
46
Case Report
An Italian 51-year-old man presented to our endoscopic unit for a colonoscopy as follow-up to a previous right colon
polypectomy for a tubulo-villous adenoma with a low-grade dysplasia, three years before. He denied any alarm
symptoms, or change in bowel habits. The examination was performed under conscious sedation by midazolam (0,07
mg/kg). The cecum was easily reached, although the 4L-PEG based BP of the right colon was suboptimal because of the
presence of copious liquid faecal residues. We try to aspirate the residues in the right colon in order to obtain an optimal
mucosal visualization. Thus, during the cecum exploration a single Ev specimen was seen protruding from fecal residues
firstly (Fig. 1) and then clearly detected (Fig. 2). When questioned for possible symptoms, he reported only the presence
of mild anal itching. Moreover, until then the presence of II grade hemorrhoids justified the symptom. A single oral dose
of 100 mg mebendazole, which was repeated 10 days later, were prescribed and a cello-tape test was performed for all
household members. A subsequent diagnosis of oxyuriasis was performed in two household members (wife and 9years-old daughter).
Fig. 1 - A white pinworm hiding among the fecal residue (black circle).
47
Fig. 2 - Adult Ev female pinworm (8-13mm) with developed reproductive organs (white area) in ascending colon. The
males, expelled immediately after copulation, are frequently not visible because they have smaller size of females (2-5
mm).
Discussion
Oxyuriasis is mainly seen in children between five and fourteen years and is frequently treated by medication. However,
this disease may also be of surgical interest because of some atypical manifestations. One of these unusual
manifestations is represented by acute or chronic appendicitis. Appendectomy is one of the most frequently performed
operations worldwide and the association of Enterobius vermicularis infestation with acute appendicitis varies from 0.2–
41.8% (12), whereas not all appendicitis are surgically treated. In a review concerning unusual histologic findings during
appendectomy, Akbulut et al (13), described a 0.5% of appendicitis caused by Ev in 80,698 appendectomies. The
parasite can creep into the appendix and cause the obstruction, a tissue reaction or actively penetrate the intestinal
wall. However, despite the presence of Ev is associated with chronic inflammatory infiltrates and eosinophilia (14, 15),
we cannot determine if inflammation is already present before infection. However, the early differential diagnosis, in
these cases can exclude surgery and post-operative complications caused by the abdominal cavity parasitic
contamination.
Although enterobiasis is mainly seen in tropical countries with lower socioeconomic levels, endoscopists practicing in
industrialized countries, must be aware of this condition in their differential diagnosis (10, 14). Furthermore, the
symptoms linked to the pinworms infestation is common to many benign pathologies of the anal region, which may
justify an endoscopic examination. Thus, the possibility of being faced with a case of undiagnosed oxyuriasis, also if
usually unexpected (16), is higher in the case of a digestive endoscopy, especially if the patient is in direct contact with
school-age children. In our case, the endoscopic diagnosis has allowed an immediate patient treatment and the
subsequent diagnosis of oxyuriasis in two household members (wife and daughter). Moreover, from the family history,
there is a high probability that the initial infection was in the 9-year old daughter.
Patients with intestinal parasitic
infestation would have undergone a previous medical examination for non-specific abdominal symptoms. The association
of anal itching, previous abdominal pain episodes, eosinophilia and proximity to a school-age child, should suggest the
presence of a parasitic infection. In this case, a cello-tape test can prevent the unjustified endoscopy or surgery.
48
Conclusions
Usually, the endoscopy cannot be considered an appropriate test for the oxyuriasis diagnosis for its lack of sensitivity.
However, considering the similarity of the symptoms manifested with other anorectal benign pathologies, the
endoscopists should always give proper weight to the factors that may predict a possible parasitic infestation.
References
1.
Cook GC. Enterobius vermicularis infection. Gut 1994;35:1159–1162.
2.
Lohiya GS, Tan-Figueroa L, Crinella FM, et al. Epidemiology and control of enterobiasis in a developmental center.
West J Med 2000;172:305–308.
3.
Brown MD. Images in clinical medicine. Enterobius vermicularis. N Engl J Med 2006;354(13):e12.
4.
Cross JH. Enteric Nematodes of Humans. In: Baron S, editor. Medical Microbiology. 4th edition. Galveston (TX):
5.
Craggs B, De Waele E, De Vogelaere K, et al. Enterobius vermicularis infection with tuboovarian abscess and
University of Texas Medical Branch at Galveston; 1996. Chapter 90.
peritonitis occurring during pregnancy. Surg Infect (Larchmt) 2009;10(6):545-547.
6.
Tandan T, Pollard AJ, MoneyDM, Scheifele,DW. Pelvic inflammatory disease associated with Enterobius
vermicularis. Archives of Disease in Childhood 2002;86(6):439–440.
7.
OkUZ, Ertan P, Limoncu E, EceA,Ozbakkaloglu B. Relationship between pinworm and urinary tract infections in
8.
Mendoza E, Jordà M, Rafel E, et al. Invasion of human embryo by Enterobius vermicularis. Arch Pathol Lab Med
young girls. APMIS 1999;107:474–476.
1987;111(8):761-762.
9.
Serpytis M, Seinin D. Fatal case of ectopic enterobiasis: Enterobius vermicularis in the kidneys. Scand J Urol
Nephrol 2012;46(1):70-72.
10. Pontone S, Magliocca FM, Cancrini G. An embarrassed patient was unmasked by the endoscopic diagnosis. A case
of Enterobius vermicularis infection in Italy. Am J Gastroenterol 2012;107(8):contents.
11. Hirai Y, Ainoda Y, Nakamura-Uchiyama F, et al. Unusual colonoscopic view of Enterobius vermicularis. Intern Med
2011;50(6):657.
12. Arca MJ, Gates RL, Groner JI, et al. Clinical manifestations of appendicial pinworms in children:an institutional
experience and a review of the literature. Pediatr Surg Int 2004,20:372-375.
13. Dahlstrom JE, Macarthur EB. Enterobius vermicularis: a possible cause of symptoms resembling appendicitis. Aust
N Z J Surg 1994, 64:692-694.
14. Akbulut S, Tas M, Sogutcu N, et al. Unusual histopathological findings in appendectomy specimens: a retrospective
analysis and literature review. World J Gastroenterol 2011;17(15):1961-1970.
15. Surmont I, Liu LX. Enteritis, eosinophilia and enterovius vermicularis. Lancet 1995, 346:1167.
16. Petro M, Iavu K, Minocha A. Unusual endoscopic and microscopic view of Enterobius vermicularis: a case report
with a review of the literature. South Med J 2005;98(9):927-929.
Corresponding Author: Stefano Pontone
Autore di riferimento: Stefano Pontone
49
Incidence of biological fluid-related accidents
among interns of a University-Hospital
INCIDENCE OF BIOLOGICAL FLUID-RELATED
AMONG INTERNS OF A UNIVERSITY-HOSPITAL
ACCIDENTS
STUDIO DI INCIDENZA SUGLI INFORTUNI A RISCHIO BIOLOGICO NEL PERSONALE
MEDICO IN FORMAZIONE SPECIALISTICA IN UNA AZIENDA OSPEDALIEROUNIVERSITARIA
Stefanati A1, De Paris P2, Nardini M2, Boschetto P1
1
Section of Hygiene and Occupational Medicine, University of Ferrara, Italy
2
Intercompany Department of Prevention and Protection, University Hospital, USL Ferrara, Italy
1
Sezione di Igiene e Medicina del Lavoro, Università degli Studi di Ferrara
2
Dipartimento Interaziendale di Prevenzione e Protezione, Azienda Ospedaliero-Universitaria,
Azienda USL di Ferrara
Citation: Stefanati A, De Paris P, Nardini M, Boschetto P. Incidence of biological fluid-related accidents among interns of
a University-Hospital. Prevent Res 2013; 3 (1):50-59.
Key words: Biological risk, occupational injuries, health care workers
Parole chiave: Esposizione a materiale biologico, infortuni occupazionali, operatori sanitari
Abstract
Background: The Hospital meant as work environment differs from most of the work environments for the plurality of
executed activities. One of the primary risks is the biological one for parenteral transmission diseases connected to
occupational injuries during health-care activity. The exposure to biological risk is very common in health workers, and
hepatitis B and C and acquired immunodeficiency syndrome are the most frequent infectious diseases.
50
Objectives: To identify, over a period of nine years (2002-2010), the prevalence and the main causes of occupational
biological exposure accidents, and the possible prevention tools, in the interns of the University Hospital of Ferrara.
Methods: We used a retrospective cohort study including a mean annual number of 537 interns (32 ± 4 years). Data on
biological incidents were collected during a surveillance programme of occupational exposure to blood and fluids.
Results: There were 331 incidents which occurred in the all period with an increase from 31 in 2002 to 41 in 2010.
Needles were the medical device most frequently involved in percutaneous injuries (82.8%), and 84.3% were blood
contacts. An interview to a subgroup of interns who had a biological incident showed important errors in their use of
personal protective equipment. Although some contacts were with infected blood, no seroconversion has been registered.
In the analysed subgroup of 20 sample subject, only 4 out of 20 doctors during specialty professional training declared to
have participated to formation courses and only 13 out of 20 were wearing the individual protection disposals (I.P.D.)
when the accident occurred. The principal reason reported by the people concerned about the lack of usage of I.P.D. was
they had underestimated the dangerousness of the maneuver they had to carry out .
Discussion and Conclusions: The study underlines the importance of HBV vaccinations and access to HIV postexposure prophylaxis. The interns are at high risk of contact with biological fluids. Prevention requires a global strategy
including the availability and the proper use of protective and safety devices, the application of the universal rules of
prevention, and training programs. More effort in preventive strategies is necessary to decrease biological accidents in
young physicians. Therefore an appropriate prevention can be reached taking into consideration all the organizational
and educational measures to reduce the accidental events concerning the health-care workers; among these measures
the organization of specific educational courses, the availability of the adequate disposals and the test of their efficacy
and liking of the users.
Other useful measures for the prevention can be adopted at the moment of medical periodic preventive examination
consisting of publicity campaign of all the accidental events and the delivery of informative.
Abstract
Introduzione: L’Ospedale inteso come ambiente lavorativo si differenzia dalla maggior parte degli ambienti di lavoro per
la molteplicità delle attività svolte, che espongono gli operatori a diversi rischi di cui il principale è il rischio biologico da
malattie a trasmissione parenterale, in particolare l’epatite B e C e l’infezione da HIV, legato ad un evento infortunistico.
Metodi: Sono stati rilevati gli infortuni biologici denunciati da una media annua di 537 medici in formazione specialistica
dell’Azienda Ospedaliero-Universitaria di Ferrara (età media ± deviazione standard: 32 anni ± 4; 66% femmine e 34%
maschi), tramite uno studio di incidenza durato 9 anni in un intervallo di tempo compreso tra il 1 gennaio 2002 ed il 31
dicembre 2010.
Risultati: Nel periodo preso in considerazione sono stati rilevati 331 infortuni biologici (media 36,8 infortuni per anno)
con un trend in aumento negli ultimi anni: 41 infortuni nel 2010 su 438 medici in formazione specialistica (9,36%),
rispetto ai 31 infortuni segnalati nel 2002 su 560 medici in formazione specialistica (5,53%). Per quanto riguarda il tipo
di esposizione nell’82,8% dei casi è stata cutanea ed il materiale biologico coinvolto era sangue nell’84,3% dei casi. Gli
agenti lesivi causa di infortunio in più della metà dei casi consistevano in ago cavo o da sutura;
punture e tagli
rappresentano il 72,4% dei casi e la modalità di infortunio più frequente (41,5%) è quella che si verifica in sala
operatoria durante gli interventi chirurgici. Infine su 331 infortuni 6 pazienti fonte erano HBV positivi (1,8%), 33 HCV
positivi (10%) e 2 HIV positivi (0,6%). Un’indagine su un campione di soggetti infortunati ha evidenziato importanti
lacune sull’uso dei dispositivi di protezione individuale (D.P.I.), l’80% non aveva ricevuto informazione/formazione
adeguata sull’utilizzo dei D.P.I.
51
Discussione e Conclusioni: Grazie all’alta adesione alla vaccinazione antiepatite B (oltre il 95% del personale) e alla
corretta applicazione del protocollo post-esposizione per HIV, nel periodo indagato non ci sono state siero-conversioni da
parte degli operatori sanitari infortunati. L’alta percentuale di infortuni nei medici in formazione specialistica è
probabilmente dovuta alla minore esperienza lavorativa e alla mancanza di adeguati corsi di formazione sull’uso corretto
dei D.P.I.. Le cause più frequenti di mancato utilizzo di D.P.I. erano la sottovalutazione della pericolosità della manovra
da effettuare e la scomodità dell’utilizzo. Devono pertanto essere messe in atto una serie di misure organizzative ed
educative per ridurre gli eventi infortunistici degli operatori, organizzando corsi di formazione specifici, mettendo a
disposizione i DPI adeguati e verificando con appositi protocolli interni il loro uso corretto, la loro efficacia e gradimento
da parte degli utilizzatori. Altre misure utili per la prevenzione possono essere attuate al momento della visita medica
preventiva e/o periodica consistenti nella sensibilizzazione relativa alla segnalazione di tutti gli eventi infortunistici e nella
distribuzione di materiale informativo.
Background
The Hospital meant as work environment differs from most of the work environments for the plurality of executed
activities. One of the primary risks is the biological one for parenteral transmission diseases connected to occupational
injuries during health-care activity.
The most frequently involved diseases are Hepatitis B (and consequently Hepatitis D), Hepatitis C and the infection from
HIV (Human Immunodeficiency Virus) (1, 2, 3, 4).
Among the principal parameters of the administration of quality the Health Care Companies have to take safety into
great consideration in order to foresee and recognize professional risks for health care workers. A qualifying aspect of
the safety education of health workers is that it is considered as a fundamental moment in the professional-educational
training, through the real awareness of the risks connected to the future professional activity. Adequate behaviours
facing the risk hardly become part of the procedure whether they were not acquired during the first phase of the
professional training (5, 6).
The aim of our study was to identify the principal causes of biological injury, and the prevention among the specialty
professional training of doctors who are more and more involved in the above mentioned injury typology. Afterwards, on
a sample of injured workers, we investigated the modality of usage of individual protection disposals (I.P.D.), with a
view to a future plan to prevent the reduction of biological incidents.
Methods
Through a study of the incidence lasted 9 years (1st January 2002 - 31st December 2010), we recorded the biological
accidents denounced by an annual mean of 537 doctors during the specialty professional training (average age: 32.6
years, ± 4.34; 66% female and 34% male). Data were collected through a special report filled out in the presence of the
injured health care worker. In addition to the personal data the following were registered: date, time, place of the
accident, a brief description of the event, the vaccinal status and the usage of I.P.D.
Afterwards we investigated the biological accidents happened during 2009, given that the highest number of incidents
happened during this year, on a sample of 20 doctors injured during their specialty professional training inside the
Azienda Ospedaliero-Universitaria of Ferrara. For this purpose we handed out a multiple choice questionnaire, based on
questions whose aim was to investigate the modality of usage of individual protection disposals (I.P.D), when the
accident occurred; this questionnaire was meant to collect the personal data, the department, the specific duty, the
detailed description of the event and the vaccinal coverage. Then for any of these variables we calculated the absolute
and percentage frequencies.
Finally
we
investigated
in
detail
the
following
parameters
in
the
above-mentioned
sample:
whether
the
formation/information about the usage of I.P.D. took place, possibility to find them easily in the different departments
and possible explanation in case they were not used.
52
The protocol about the biological risk in force in the Azienda Ospedaliero-Universitaria gives the exposed health care
workers an appropriate procedure about the handling of the biological accidents and the post exposition prophylaxis
(PEP) which contemplates a serological test in 0, 1, 3 and 6 months since the accident.
Results
Since January 2002 to 31st December 2010 there were 331 biological accidents (average 36,8 accidents per year) with
an increasing trend in the last two years, respectively 44 accidents in 2009 (8.94%) and 41 in 2010 (9.36%) in
comparison with the 31 ones reported in 2002 and 2003 (respectively 5.53% and 5.52%). The data refer to the total
amount of doctors during the specialty professional training attending the different Schools of Specialization including
those where the risk of biological accident is quite low. (Figures 1 and 2).
Fig. 1 - Number of biological accidents from 2002 to 2010 in interns at the University-Hospital of Ferrara
N° infortuni biologici nei Medici in Formazione
Specialistica dal 2002 al 2010
600
561
560
561
561
560
560
544
492
500
400
438
N° infortuni 300
200
100
0
N° Infort.
Tot. Spec.
31
31
37
41
32
36
38
44
41
Anno Anno Anno Anno Anno Anno Anno Anno Anno
2002 2003 2004 2005 2006 2007 2008 2009 2010
Anni monitorati
Fig. 2 - Percentage of biological accidents from 2002 to 2010 in interns at the University-Hospital of Ferrara
% infortuni biologici nei Medici in formazione specialistica
10
8,94
9,36
9
7,32
8
7
6
% infortuni
6,98
6,59
5,53
5,52
6,42
5,71
5
4
%
3
2
1
0
Anno
2002
Anno
2003
Anno
2004
Anno
2005
Anno
2006
Anno
2007
Anno
2008
Anno
2009
Anno
2010
Anni monitorati
53
Considering the everyday practice the effective number of exposed staff is lower and mostly concentrated among the
medical and surgical disciplines.
As to the type of exposure in 82.8% of cases it was cutaneous and blood was the biological involved material in 84.3%
of cases (Table 1). The harmful agents which caused the accidents in more than half of cases consisted of hollow or
suture needle (Table 2).
In reference to the distribution of accidents according to the tipology, it is evident that needle pricks and cuts represent
the 72.4% of cases, while squirt or contamination are responsible for less than a quarter of the accidents (Table 3).
Moreover the 41.5% of the accidental events happens during the surgical interventions and, unfortunately, 0.6% of
health care workers' accidents happen while recapping needles (Table 4). Finally, as quoted in Table 5, out of 331
accidents, 6 source patients were HBV positive (1.8%), 33 HCV positive (10%) and 2 HIV positive (0.6%). The 4.5% of
accidents happened by an unknown source.
During all the years taken into consideration there were not serum
conversions by the involved health care workers, thanks to the high adhesion to anti-hepatitis B vaccination (more than
95% of the staff) and to the right application of the post-exposure protocol for HIV.
In the analysed subgroup of 20 sample subject, only 4 out of 20 doctors during specialty professional training declared
to have participated to formation courses and only 13 out of 20 were wearing the I.P.D. when the accident occurred.
The principal reason reported by the people concerned about the lack of usage of I.P.D. was they had underestimated
the dangerousness of the maneuver they had to carry out (Table 6).
Table 1 - Accidents distribution by type of biological exposure and material
ESPOSIZIONE
N°
%
Cute
274
82,8
Mucosa
49
14,8
Cute e Mucosa
8
2,4
Totale
331
100%
MATERIALE BIOLOGICO
N°
%
Sangue
279
84,3
Sangue misto ad altro materiale
50
15,1
Saliva
1
0,3
Urina
1
0,3
Totale
331
100%
54
Table2 - Devices involved in the accidents
AGENTE LESIVO
N°
%
Ago siringa
38
11,5
Ago chirurgico (da sutura)
120
36,2
Ago cannula/Abocath/CVC
17
5,1
Altro ago/tagliente
75
22,6
Bisturi
27
8,1
Elettrobisturi
3
0,9
Ferro chirurgico
6
1,8
Guanto rotto
4
1,2
Altro
41
12,4%
Table 3 - Accidents distribution by type
LESIONE
N°
%
Puntura
215
64,9
Schizzo
57
17,2
Imbrattamento
25
7,6
Taglio
25
7,6
Graffio
3
0,9
Escoriazione
4
1,2
Ustione
2
0,6
Totale
331
100%
55
Table 4 - Work situations at risk of biological accidents
Modalità
N°
%
Durante intervento chirurgico
137
41,5
Lavando elettrobisturi
27
8,1
Suturando ferita
17
5,1
Causa altro operatore
8
2,4
Posizionando CVC
7
2,1
Ago in luogo non appropriato
4
1,2
Ago sporgeva dal contenitore
3
0,9
Dopo prelievo ematico
6
1,8
In corso di autopsia
5
1,5
Reincappucciando l’ago
2
0,6
Altro
115
34,8
Totale
331
100%
Table 5 - Serologic data of the source patient (when identified)
PAZIENTE FONTE
N°
%
Consenziente
316
95,5
Non consenziente
-
-
Sconosciuto
15
4,5
Totale
331
100%
SIEROLOGIA PAZIENTE
N°
%
HBV-HCV-HIV negativo
275
83,1
HBV positivo
6
1,8
HCV positivo
33
10,0
HIV positivo
2
0,6
Sconosciuto
15
4,5
Totale
331
100%
56
Table 6 - Interview results of the intern subgroup on the proper use of personal protective equipment
Quesiti
M.F.S. num.
M.F.S. %
(n=20)
Informazioni
sul
corretto uso D.P.I.
SI
4
20
NO
16
80
SI
4
20
NO
16
80
M.F.S. num.
M.F.S%
(n=20)
(su
Formazione uso D.P.I.
7
che
non
avevano utilizzato
DPI).
Mancato uso D.P.I.
Sottovaluta manovra
4
57,1
Scomodità utilizzo
3
42,9
Non disponibili
0
0
Manovra non prevista
0
0
Despite the decrease of the absolute number of doctors during specialty professional training, who attended the Schools
of Specialization of the University of Ferrara, due to the different regulations issued in various years, the percentage of
accidents has increased twice as much from 5.53% of 2002 to 9.36% of 2010. Probably this has to be correlated to the
fact that, since the very beginning of the course, according to the recent regulations of the Schools of Specialization
post-graduate Medicine doctors are involved in practical activities with direct responsibility.
The most frequent typology of incident is the percutaneous exposure caused mainly by the prick of hollow or suture
needle. Blood is the biological material with which the health care workers often come into contact, given that as a
consequence of most of the tasks connected with the health care these situations of risk are among the most common
both in the surgical and medical departments (4, 7, 8, 9).
The verification that we did of a high number of biological injuries in doctors during specialty professional training
confirm the previous reports by Saia M et al. (9) of a higher annual index of incidents concerning this group of doctors in
comparison with the specialist doctors. The brief work experience of the staff in training and the peculiarity of the work
typology linked to the different hospital departments can play a prominent role as a cause of incident, as proved by
several authors (5, 6, 7, 8, 10, 11, 12). Moreover Sacchi M et al.(12) demonstrate that the accidental phenomenon is
linked to the old age of the injured health care workers, in fact the highest number of contacts take place in the group
composed by the obstetric staff with length of service of less than five years.
Taking into consideration that: 1) cuts and pricks represent the most frequent event of accident; 2) the suture activity
inside the operating theatre has the major risk, the reported data of the present study are in line with what has reported
by literature on this topic. The Gruppo di Studio Italiano sul Rischio Occupazionale da HIV (Italian Group of Study about
the Occupational Risk by HIV) fully demonstrated that percutaneous exposure incidents represent the most frequent
method of biological injury and that syringes and suture needles are the most frequently involved (4, 7, 9, 10, 13).
As it is possible to see in Table 5, despite there were 6 injuries with an HBV-positive patient, 33 with an HCV-positive
one and 2 with an HIV-seropositive patient, there were no case of seroconversion of the health care workers. Therefore
it is necessary to incentivize the personnel about the application of the prevention standards present in D.M. 28/9/1990
(14) given that the respect of universal precautions and the post-exposure prophylaxis contribute to decrease of more
57
than 1/3 the consequences of biological-risk incidents, in case it is not possible a primary prevention through vaccination
(9, 15, 16, 17).
An aspect emerged from the sample investigation in the subgroup of the doctors in specialty professional training (Table
6) interviewed about the right usage of I.P.D.: the non-optimal adhesion to the indications established by the current
regulations; in particular the 80% of doctors in specialty professional-educational training declared they were not given
the appropriate information and an adequate education about the right use of I.P.D. Approximately a third were not
wearing an appropriate I.P.D. when the accident occurred and the 57.1% declared they they had underestimated the
dangerousness of the maneuver they had to carry out, while the 42.9% considered uncomfortable the use of I.P.D. In
particular lateral protection safety spectacles were subject to mist and face masks slipped out of their position causing a
frequent and uncomfortable repositioning of the devices. The non-elevated adhesion to the I.P.D. usage is emphasized
also by the other authors who report a percentage of 45% of non-usage of I.P.D. among the injured of their case study
(12).
In our Azienda Ospedaliero-Universitaria, to provide for this situation, a procedure about the right handling of the
individual protection disposals was prepared and inserted in the intranet site; a tutor is the responsible of delivering and
give the worker the specific training of about the protection disposals. Moreover, through an apposite form, the healthcare worker can send remarks about the quality and the ergonomic features of I.P.D. The discomfort when using the
I.P.D. represented the 42.9% of reasons why the disposals were not used in our sample. Finally in the hospital corporate
intranet site the forms the related procedure to communicate an biological incident are available; the aim is to have a
more comfortable and fast denunciation of the event. We hope this could contribute to the reduction of the underreporting phenomenon widely related in literature (6, 10, 18). We could test the efficacy of these interventions in two
years through an exam of the results.
Therefore an appropriate prevention can be reached taking into consideration all the organizational and educational
measures to reduce the accidental events concerning the health-care workers; among these measures the organization
of specific educational courses, the availability of the adequate disposals and the test of their efficacy and liking of the
users.
Other useful measures for the prevention can be adopted at the moment of medical periodic preventive examination
consisting of publicity campaign of all the accidental events and the delivery of informative.
****************************************************
NO POTENTIAL CONFLICT OF INTEREST RELEVANT TO THIS ARTICLE WAS REPORTED
58
References
1.
Daglio M, Sacchi M, Feletti T, et al. Infortuni a rischio biologico nel personale sanitario: analisi epidemiologica
descrittiva nel decennio 1994-2003. G Ital Med Lav Ergon 2006;28:457-465.
2.
D’Orso MI, Colombo P, Binelli L, et al. L’introduzione di dispositivi di prevenzione di puntura accidentale (ago protettivo
per prelievo venoso sottovuoto) in una azienda ospedaliero-universitaria: valutazione dell’impatto preventivo sul
rischio biologico degli operatori. G Ital Med Lav Ergon 2008;30(3 suppl. 2):66-67.
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Gatto MR, Bernardi F, Bandini L, Prati C. Esposizione occupazionale a rischio biologico nel Dipartimento di Scienze
Odontostomatologiche: risultati di uno studio di sorveglianza di 10 anni. Med Lav 2010;101:218-227.
4.
Puro V, De Carli G, Segata A, et al. Update on the subject of epidemiology of blood-transmitted occupational
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Petrucci C, Alvaro R, Cicolini G, et al. Percutaneous and mucocutaneous exposures in nursing students: an italian
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exposure to bloo-borne pathogens in health care workers: strategies for prevention. Med Lav 2007;98:145-155.
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Puro V, De Carli G, Petrosillo N, Ippolito G. Risk of exposure to bloodborne infection for Italian healthcare workers, by
job category and work area. Studio Italiano Rischio Occupazionale da HIV Group (SIROH). Infect Control Hosp
Epidemiol 2001;22(4):206-210.
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Saia M, Castoro M, Barra S, et al. Rischio biologico per il personale medico di sala operatoria. Ig Mod 2002; 117:191-
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Davanzo E, Frasson C, Morandin M, Trevisan A. Occupational blood and body fluid exposure of university health care
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Naghavi SH, Sanati KA. Accidental blood fluid exposure among doctors. Occup Med 2009;59:101-106.
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Sacchi M, Daglio M, Feletti T, et al. Infortuni a rischio di malattie a trasmissione ematica nel personale ostetrico:
analisi di una casistica ospedaliera. Med Lav 2007;98(1):64-72.
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Gabutti G, Garra L, Giordano C, et al. Sorveglianza delle esposizioni professionali a materiale biologico contaminato da
HIV, HCV e HBV negli operatori sanitari. Ig Mod 2000;113:391-400.
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Decreto Ministeriale 28 settembre 1990. Norme di prevenzione dal contagio professionale da HIV nelle strutture
sanitarie ed assistenziali pubbliche e private. G.U. del 8 ottobre 1990, n.235.
15.
Cardo DM, Culver DH, Ciesielski CA, et al. A case-control study of HIV seroconversion in health care workers after
percutaneous exposure. Center for Disease Control and Prevention Needlestick Surveillance Group. N Engl
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1997;337(21):1485-1490.
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Gabriel J. Reducing needlestick and sharps injures among healthcare workers. Nurs Stand 2009;23:41-44.
17.
Wicker S, Cinati J, Berger A, et al. Determination of risk of infection with blood-borne pathogens following a
needlestick injury in hospital workers. Ann Occup Hyg 2008;52:615-622.
18.
Kessler CS, McGuinn M, Spec A, et al. Underreporting of blood and body fluid exposures among health care students
and trainees in the acute care setting: a 2007 survey. Am J Infect Control 2011;39:129-134.
Corresponding Author: Armando Stefanati
Section of Hygiene and Occupational Medicine, University of Ferrara, Italy
Autore di riferimento: Armando Stefanati
Sezione di Igiene e Medicina del Lavoro, Università degli Studi di Ferrara
59

volume 3 number 01 - Prevention and Research

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