Incidence, clinical outcome, and risk stratification of ventilator-associated pneumonia a prospective cohort study

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1 IJCCM October-December 2003 Vol 7 Issue 4 Indin J Crit Cre Med October-December 2005 Vol 9 Issue 4 Originl Article Incidence, clinicl outcome, nd risk strtifiction of ventiltor-ssocited pneumoni prospective cohort study Pnwr Rkshit, Vidy S. Ngr, Alk K. Deshpnde Abstrct Context nd Aim: Ventiltor-ssocited pneumoni (VAP) remins to be the commonest cuse of hospitl morbidity nd mortlity in spite of dvnces in dignostic techniques nd mngement. This project ims to study the vrious risk fctors nd the common microbil flor ssocited with VAP. It lso evlutes the use of APACHEIII scores for prognostiction. Study Design: A prospective cohort study ws conducted over 1 yer in medicl criticl cre unit (CCU) of tertiry-cre teching hospitl. Methods nd Mteril: VAP ws dignosed using the clinicl pulmonry infection score (CPIS) of more thn 6. The study cohort comprised 51 ptients. All CCU ptients requiring mechnicl ventiltion for more thn 48 h formed the study group. Sttisticl Anlysis Used: Univrite nlysis, χ 2 -test, nd pired t-test. Results: Twentyfour out of fifty-one cses developed VAP. These cses hd n verge APACHEIII score of more thn 55 on dmission to criticl cre unit (CCU). They needed prolonged mechnicl ventiltion nd hd lower PO /FiO rtio s compred with the remining ptients who did not develop VAP. Pseudomons eroginos 2 2 ws the commonest nd most lethl orgnism. The mortlity in the VAP group ws 37% nd correlted very well with higher APACHEIII scores on dmission. Conclusions: Longer durtion of mechnicl ventiltion nd the need of reintubtion re ssocited with proportionte rise in the incidence of VAP. Deteriorting PO2/FiO rtio correlted well with the onset of VAP. Higher APACHEIII scores on dmission 2 strtify the mortlity risk. Key Words: APACHE III (Acute Physiology, Age nd Chronic Helth Evlution) Scores, Comorbid illnesses, Mechnicl ventiltion, Mortlity, Nonsurvivors, PO /FiO rtio, Ventiltor-ssocited pneumoni 2 2 Introduction Ventiltor-ssocited pneumoni (VAP) refers to bcteril pneumonis developing in ptients who hve been receiving mechnicl ventiltion (MV) for t lest 48 h. [1] VAP is the commonest compliction ssocited with MV reported t the rte of 1 3% per dy of MV. [2] Prevlence rnges from 10% to 65% in tertiry-cre hospitls with pri pssu rise in cse ftlity rtes of more thn 20% ccording to reported studies. [3] Incriminting pthogens vry mong hospitls. [4] Therefore, incidence of VAP nd the ssocited locl microbil flor needs to be studied in ech setting so s to guide more effective From: Deprtment of Medicine, Grnt Medicl College, Sir J. J. Group of Govern- nd rtionl utiliztion of ntimicrobil gents. [4] ment Hospitls, Mumbi, Indi Correspondence: The precise dignosis of pneumoni is often difficult in Pnwr Rkshit, A-1203, Eterni, Hirnndni Grdens, Powi, Mumbi , Indi. E-mil: rkshitpnwr@hotmil.com criticlly ill ptients. Purulent sputum my follow intub- Free full text vilble from 211

2 Indin J Crit Cre Med October-December 2005 Vol 9 Issue 4 tion or lekge of orophryngel secretions round the rtificil irwy. Furthermore, chest roentgenogrphic chnges consistent with pneumoni my be cused by pulmonry edem, pulmonry infrction, telectsis, or cute respirtory distress syndrome. [5] Lck of n unequivocl gold stndrd complictes the issue of deciding the best dignostic technique for suspected VAP. Although the sensitivity of clinicl dignosis of VAP is high, the specificity is low. But VAP is one entity in which subjective clinicl impression ppers to be more ccurte thn set of objective criteri. [6] APACHEIII score, which is further refinement of APACHE system, my help in strtifying hospitl mortlity risk, which my impct on the scope nd intensity of tretment. This study ws designed to determine the incidence of VAP, the ssocited risk fctors, the custive microbil flor, nd the role of APACHEIII in prognostiction of ptients t the time of dmission to CCU in tertirycre centre. Mterils nd Methods The study spnned period of 1 yer. All cses dmitted in CCU in pst 1 yer requiring MV for longer thn 48 h formed the study cohort. Ptients who were lredy on MV before dmission to CCU or those who died within 48 h of strting MV were excluded. VAP ws considered s subjective clinicl impression. It ws further substntited using clinicl pulmonry infection score (CPIS). CPIS of greter thn 6 ws used s dignostic criteri for VAP. [7] Pugin et l. [7] developed CPIS score bsed on giving 0 2 points ech for fever, leukocyte count, oxygention, quntity, nd purulence of trchel secretions, type of rdiogrphic bnormlity, nd results of sputum culture nd Grm stin. The bseline evlution of ll the cses in this study included the ptient-relted fctors such s ge, concomitnt diseses, immunosuppression, indiction of MV, the rtio of PO2 to FiO2 prior to onset of VAP, nd severity of illness bsed on APACHEIII scoring system. IJCCM October-December 2003 Vol 7 Issue 4 On dmission to CCU, the entire cohort ws llotted scores for their ge, chronic helth sttus, physiologic prmeters, cid bse sttus, nd neurologicl sttus, bsed on APACHEIII scoring system. Totl APACHEIII score ws deduced by dding ll these scores. [8] The risk fctors included reintubtion, use of chemicl prlysis, need for dilysis, durtion of MV, nd durtion of CCU sty. Sttisticl Anlysis The study cohort ws clssified in four groups: VAP, non-vap, survivors, nd nonsurvivors. After evluting ll the bove-mentioned fctors, the dt were subjected to the univrite nlysis using the chi-squre test. The level of significnce ws set t P<0.05. Results The study cohort comprised 51 ptients with 29 (56.9%) mles nd 22 (43.1%) femles. The men ge of ptients in this cohort ws 34 yers; 24 out of 51 ptients (47%) developed VAP during CCU sty. The incidence rte of VAP in our study ws 26 per 1000 ventiltor dys. Tble 1 shows the clinicl spectrum of our cses tht includes 21 ptients with vrious neurologicl disorders, 6 cses of tropicl diseses, 12 cses of poisonings, 12 cses of metbolic disorder, 3 cses of sepsis, nd others. Some of our ptients hd multiple disorders. The incidence of VAP ws greter either in ptients with diseses necessitting prolonged MV (e.g., Guillin-Brre syndrome, tetnus, orgnophosphorus poisoning, etc.), or in ptients with those diseses tht predispose to pulmonry infection (such s sepsis, tropicl diseses, or immunosuppression) (Tble 1). It is lso significnt to note tht the incidence of VAP ws considerbly low in ptients with diseses which presumbly, hd unffected lungs before dmission to CCU, for exmple, meningoencephlitis (12%), hydrocephlus (0%), snke bite (0%), etc. (Tble 1). Tble 2 shows the distribution of onset of VAP for the study cohort. The totl (n) number of ptients on MV who were being followed during ech time period is given long with the percentge of those people who did not develop VAP. Also given is the number of cses with onset of VAP during ech time period. This tble clerly 212

3 IJCCM October-December 2003 Vol 7 Issue 4 Indin J Crit Cre Med October-December 2005 Vol 9 Issue 4 Tble 1: Clinicl spectrum Diseses n (no. of VAP Non-VAP ptients) CNS disorders Meningoencephlitis 8 1 (12%) 7 GBS/AIDP 8 4 (50%) 4 Mystheni grvis 1 1 NA Hydrocephlus/SAH 4 NA (0%) 4 Tropicl diseses Complicted mlri 2 1 (50%) 1 Leptospirosis Tetnus 3 2 (67%) 1 Poisoning OP poisoning 11 6 (55%) 5 Snke bite 1 - (0%) 1 Metbolic ARF/CRF/RTA 10 5 (50%) 5 DM/DKA 2 1 (50%) 1 Miscellneous Shock/sepsis 3 2 (67%) 1 Pncretitis Pulmonry fibrosis Totl (n) is more thn 51 s some ptients hd multiple disorders. Percentge in prentheses denotes percentge of ptients with the specified disese, who developed VAP. CNS, centrl nervous system; GBS, Guillin- Brre syndrome; AIDP, cute inflmmtory demyelinting polyneuropthy; SAH, subrchnoid hemorrhge; OP, orgnophosphorous; ARF, cute renl filure; CRF, chronic renl filure; RTA, renl tubulr cidosis; DM, dibetes mellitus; DKA, dibetic ketocidosis. Tble 2: Distribution of onset of VAP for the cohort nd cumultive risk of VAP with durtion of MV Dys of Totl (n) No. of ptients No. free Free of VAP MV with onset of VAP of VAP (%) > The time period (26 45) is much longer compred with others. demonstrtes the decline in percentge of ptients free of VAP s the durtion of MV increses. Ptients who developed VAP within 96 h of MV were ctegorized s hving erly-onset VAP nd those who developed fter 96 h were clssified s lte-onset VAP. Eight ptients developed erly-onset VAP nd 16 (31%) ptients developed lte-onset VAP. The incidence of VAP incresed with the durtion of MV. The men durtion of MV in cses without VAP ws 13.5 dys s ginst 23.4 dys in ptients with VAP (P< 0.05). In ddition, it my be noted tht the men durtion of MV in ptients with lte-onset VAP ws dys (P<0.005). Thus, it emphsizes direct correltion between the durtion of MV nd development of VAP. The verge length of sty in CCU for ptients who developed VAP ws 28 dys (σ=18), wheres the verge for non-vap ptients ws pprecibly low t 19 dys (σ=13) (P<0.05). Tble 3 shows correltion between ptient relted fctors nd Incidence of VAP. It lso highlights the ssocition between the severity of illness, ssessed by APACHEIII scores on dmission, nd VAP. Ptients with VAP hd n verge APACHEIII score of 55.1, compred with non-vap group, whose score ws (P< 0.05) The comorbid conditions plyed mjor role in CCU complictions. Ptients who developed VAP were more likely to be suffering from conditions cusing immunosuppression, such s chronic renl filure, dibetes mellitus, nd steroid therpy. These ptients were presumbly hrbouring infections prior to dmission. PO 2 rtio ws compred in both the groups (VAP nd non-vap) nd ws significntly lower in VAP group (P< 0.001). PO 2 rtio ws ssessed dily during the course of ventiltory support nd it ws observed tht the rtio dropped t lest h prior to onset of clinicordiologic picture suggestive of VAP. Ptients who were dignosed ARDS on bsis of PO 2 rtio being less thn 200, were excluded from this comprison of PO 2 rtio. Thus decline in PO 2 rtio ws found to be n erly indictor of the onset of VAP. Tble 4 reltes the helth-cre fctors to the VAP. Out of 24 cses, who were reintubted, 19 developed VAP (P<0.001), wheres out of 11 ptients, who hd erly nd plnned trcheostomy, only one developed VAP (P<0.005). Tble 5 revels the incriminting microbil flor. Grmnegtive orgnisms were isolted from 26 out of 32 cultures. Most common offending orgnism isolted in cses with Erly-onset VAP is Pseudomons eroginos Tble 3: Ptient-relted fctors Non-VAP VAP P Comorbid fctors (n = 13) 6 7 Immunosuppression/infection (n= 7) PO 2 rtio <0.001 APACHEIII score Dt expressed s no. unless specified. n denotes number of ptients. Few ptients were excluded s they were suspected/proven cses of ARDS. Tble 4: Fctors relted to course of cre Non-VAP VAP P Dilysis (n= 11) 5 6 Reintubtion (n= 24) 5 19 <0.001 Trcheostomy (n= 11) 10 1 <0.005 Chemicl prlysis (n=8)

4 Indin J Crit Cre Med October-December 2005 Vol 9 Issue 4 IJCCM October-December 2003 Vol 7 Issue 4 Tble 5: Custive orgnisms nd VAP Orgnisms Erly-onset Lte-onset Totl VAP VAP P. eroginos Klebsiell pneumonie E. coli nd Proteus sp Acinetobcter sp. 2 2 Stphylococcus ureus 6 6 n denotes number of ptients who required the specified tretment. (60%) followed by Klebsiell nd Escherichi coli. In ptients with lte-onset VAP, most common orgnism isolted ws Stphylococcus ureus (26%), followed closely by P. eroginos, Klebsiell, E. coli, nd Acinetobcter. The overll mortlity rtes were highest with Pseudomons (42%), in spite of dequte nd proper ntimicrobil therpy, followed by S. ureus (33%) nd others. Mortlity ws observed to be low in ptients who were suffering from potentilly remedible conditions, for exmple, tropicl infections, orgnophosphorus poisoning, Guillin-Brre syndrome, etc. However, much poorer prognosis ws found to be ssocited with conditions such s sepsis/shock (67%), pncretitis (100%), nd conditions with CNS complictions (e.g., hydrocephlus [75%], cerebrl mlri [50%], or meningoencephlitis [50%]) [Tble 7]. Tble 6 shows the clinicl outcome nd its reltion with the fctors relted to ptient nd their course of cre, e.g., ge, presence of comorbid fctors, infection or immunosuppression, reintubtion, trcheostomy, nd APACHEIII scores on dmission. Nineteen ptients out of fifty-one (37%) succumbed while being treted in CCU. Ptients who died were slightly older in ge (men 38.7 yers) s ginst the survivors (men 31.1 yers). Five ptients were more thn 60 yers old nd none of them could survive. Thus, mortlity ws significntly higher in older ge groups. Mortlity ws lso higher in the VAP group (Tble 8), though the difference ws not sttisti- Tble 6: Mortlity nd fctors relted to course of cre Survivors Nonsurvivors P (32 ptients) (19 ptients) Men ge (yers) Comorbid fctors (n= 13) 4 9 <0.01 Immunosuppression/ 4 3 infection (n= 7) APACHEIII (SD) 40.2 (22) 65 (18.4) <0.001 Dilysis/PEEP (n= 11) 4 7 <0.05 Reintubtion (n= 24) Trcheostomy (n= 11) 10 1 <0.005 Tble 7: Distribution pttern of diseses nd mortlity Diseses n (no. of Nonsurvivors Survivors ptients) CNS disorders Meningoencephlitis 8 4 (50%) 4 GBS/AIDP 8 1 (12%) 7 Mystheni grvis 1 1 Hydrocephlus/SAH 4 3 (75%) 1 Tropicl diseses Complicted mlri Leptospirosis 1-1 Tetnus 3-3 Poisoning OP poisoning 11 2 (18%) 9 Snke bite 1 1 Metbolic ARF/CRF/RTA 10 4 (40%) 6 DM/DKA 2 2 Miscellneous Shock/sepsis 3 2 (67%) 1 Pncretitis 2 2 (100%) Pulmonry fibrosis 1 1 Dt expressed s number of ptients ssocited with given fctors unless specified. Totl (n) is more thn 51 s some ptients hd multiple disorders. Percentge in prenthesis denotes percentge of ptients with the specified disese, who did not survive. Tble 8: VAP nd clinicl outcome Totl Survivors Nonsurvivors VAP (37.5%) Non-VAP (26%) n = Four deths ttributed to ARDS were excluded, nd so n = 47. clly significnt. The ttributble risk percentge of VAP ws 30.4% nd the reltive risk ws This nlysis (Tble 6) demonstrted tht mortlity ws significntly high in ptients with comorbid illnesses (P<0.01) such s hypertension, chronic renl filure, metsttic mlignncies, obesity, etc. Mortlity ws found to be predominntly relted to underlying severity of disese which ws ssessed by APACHEIII scores within first 24 h of dmission to CCU. Men APACHEIII score on dmission in survivor s group ws 40.2, wheres it ws significntly higher t 65 in nonsurvivors (P<0.001) (Tble 6). Significntly (P< 0.005) higher survivl rtes were found in cses tht hd erly nd plnned trcheostomy, s compred with those who needed reintubtions. Discussion VAP is the commonest nosocomil infection mongst ptients receiving MV in CCU. The incidence of VAP in our setting ws 47% nd the incidence rte of VAP in our study ws 26 per 1000 ventiltor dys. 214

5 IJCCM October-December 2003 Vol 7 Issue 4 Indin J Crit Cre Med October-December 2005 Vol 9 Issue 4 Tble 9 shows the incidence of VAP, reported by recent studies (Torres, Kollef, nd Fgon), rnging from 15.5% by Kollef et l. to 27.5% by Fgon et l. However, it my be noted tht both these studies were of 2 nd 5 yers durtion, respectively, with much lrger number of ptients studied, viz., 277 by Kollef nd 1118 by Fgon. The totl number of cses in our study is smll. The higher incidence of VAP in our study could lso be owing to the presence of comorbid conditions. The ptients who succumbed were seriously ill with conditions such s septic shock, pncretitis, cerebrl mlri, etc. The helth-seeking behvior of our ptients is different compred with tht in developed world. Owing to limited resources, ptients seek medicl help only when it is bsolutely inevitble. By the time he is referred to the tertiry-cre centre, his underlying condition is well dvnced nd my be irreversible. This my necessitte longer durtion of MV, which is directly proportionl to development of VAP. The other most importnt fctor leding to higher incidence of VAP in our set-up my be ttributed to the pucity of nursing stff tht leves lcune in the idel ptient cre. The ptient to nurse rtio in our CCU set-up is 4:1, the desired rtio being 1:1. Reintubtion hs resulted in very high incidence of VAP. An erly nd plnned trcheostomy hs shown significnt reduction in occurrence of VAP, which is lso dvocted by mny other reports in literture. Other risk fctors identified were immunosuppression, use of chemicl prlysis, nd dilysis. This study lso signifies tht decline in PO 2 / FiO 2 rtio is n erly indictor of onset of VAP. In summry, the significnt risk fctors for development of VAP were prolonged durtion of MV, higher APACHEIII scores on dmission signifying severe illness nd reintubtion. Other positive risk fctors identified were presence of comorbid conditions cusing immunosuppression/ infection, use of chemicl prlysis, nd use of dilysis during the course of CCU sty. The ptients who cquired VAP hd longer lengths of CCU sty s well s greter hospitl mortlity rtes (37%). In our study, VAP ws not independently ssocited with mortlity, though mortlity rte ws higher in ptients with VAP (Tble 8). Mortlity ws predominntly ssocited with underlying severity of disese, presence of comorbid fctors, nd older ge groups. APACHEIII scores within first 24 h of dmission to CCU were used to ddress the underlying severity of illness. Ptients who developed VAP hd sttisticlly higher APACHEIII score t dmission (55) s compred with ptients without VAP (42). Likewise, ptients who died hd even higher scores (65), (P<0.001). Thus, APACHEIII score t the time of dmission ws found to be useful prmeter to prognosticte ptients on rrivl nd lso during their course of sty. Tble 10 demonstrtes tht our CCU hs prticulrly high incidence of pneumoni cused by Pseudomons nd Klebsiell s compred with other studies. Also, we found tht incidence of polymicrobil flor ws higher in trchel spirte culture. Furthermore, mortlity rtes were higher with Pseudomons followed by Stphylococcus nd Klebsiell. Also, it ws observed tht pthogens isolted were potentilly ntibiotic resistnt. We could not study Susceptibility profile in detil owing to pucity of clinicl microbiology support nd unffording Tble 10: Orgnisms responsible for VAP ( comprison with other studies) [9] Fgon et l., Torres et l., Our study No. of episodes of pneumoni Technique PSB PSB, BAL Trchel spirte Threshold (CFU/ml) 10 [3] 10 [3] 10 [6] Grm-negtive bcteri No. (%) No. (%) No. (%) P. eroginos 16 (31) 7 (28) 11 (46) Acinetobcter 8 (15) 6 (24) 2 (8) Proteus 8 (15) - 3 (13) E. coli 4 (8) 3 (12) 3 (12) Klebsiell 2 (4) 3 (12) 7 (29) Grm-positive bcteri S. ureus 17 (33) 5 (20) 6 (25) S. pneum. 3 (6) 1 (4) - Polymicrobil flor 21 (40) 10 (40) 13 (54) CFU, colony-forming units. Sum of % exceeds 100% owing to isoltion of multiple orgnisms in culture. Tble 9: Incidence nd mortlity rte of VAP [9] ( comprison with other studies) Authors Study yers No. of ptients studied Incidence of VAP (%) Dignostic criteri Mortlity rtes (%) Kerver et l Clinicl 30 Torres et l Clinicl, PSB 33 Kollef et l Clinicl 37.5 Fgon et l PSB, BAL 53 Our study Clinicl

6 Indin J Crit Cre Med October-December 2005 Vol 9 Issue 4 ptients but, recounting our experience, our findings re s follows. Pseudomons ws isolted in 11 smples nd ws found to be mximlly susceptible to meropenem nd cefpirome. Pseudomons showed fvorble susceptibility pttern to pipercillin, cefoperzone-sulbctm, nd mikcin wheres it ws firly resistnt to drugs such s levofloxcin, ciprofloxcin, nd ceftzidime. K. pneumonie ws isolted in seven smples nd showed mximl susceptibility to meropenem, cefpirome, nd cefoperzonesulbctm. Klebsiell ws modertely susceptible to pipercillin nd ciprofloxcin nd ws highly resistnt to moxicillin-clvulnte, cefotxime, ceftrixone, nd ceftzidime. S. ureus ws isolted in six smples nd ll isoltes were resistnt to methicillin nd moxicillinclvulnte. Stphylococcus showed excellent sensitivity to vncomycin nd teicoplnin. Linezolid ws used only in one ptient who did not respond well to vncomycin. Conclusions We rrive t the following conclusions: 1. The incidence of VAP is directly proportionl to the durtion of MV. 2. Comorbid conditions nd reintubtion contribute to development of VAP. 3. APACHEIII score on dmission is useful prmeter for prognostiction of ptients. 4. A decline in PO 2 rtio cn help in erly suspicion of VAP. IJCCM October-December 2003 Vol 7 Issue 4 5. Erly nd plnned trcheostomy is ssocited with lower incidence of VAP nd low mortlity rtes. 6. Grm-negtive microbes followed by methicillin resistnt Stphylococcus ureus re commonest incriminting orgnisms. References 1. Pingleton SK, Fgon JY, Leeper KV. Ptient selection for Clinicl investigtion of VAP. Chest 1992;102; George DL. Epidemiology of nosocomil pneumoni in MICU. Med Clin Chest Med 1995;16: Kollef MH, Silver P, Murphy DM. The effect of VAP in determining mortlity. Chest 1995;108: S Borges M, Corre H. Vritions in etiology of VAP. Respirtor Crit Cre Med 1999;160: Fgon JY, Chstre J, Domrt Y, Trouillet JL, Pierre J, Drne C, et l. Nosocomil Pneumoni in ptients receiving continuous mechnicl ventiltion. Am Rev Respirtor Dis 1989;139: Fgon J, Chstre J. Evlution of clinicl judgement in identifiction nd tretment of nosocomil pneumoni in ventilted ptients. Chest 1993;103: Pugin J, Auckenthler R, Mili N. Dignosis of VAP. Am Rev Respirtor Dis 1991;143: Knus WA, Wgner DP, Drper EA, Zimmermn JE, Bergner M. The APACHEIII prognostic system: Risk prediction of hospitl mortlity for criticlly ill hospitlized dults. Chest 1991;100: Chstre J, Fgon JY. Ventiltor-ssocited pneumoni, Principles of Criticl Cre; pp