Interactive case: Approaching intra-abdominal sepsis Ph Montravers Department of Anaesthesiology and Critical Care Medicine CHU Bichat Claude Bernard, APHP Université Paris VII Denis Diderot-Sorbonne Cite Paris, France
Disclosure Expert/Advisor or lectures for the following companies Astellas Astra-Zeneca Cubist Gilead Merck Sharp Dohme Chibret Pfizer
Mrs L. 56 year old Admitted to hospital with severe abdominal pain Past medical history : Heavy smoker (40 g/d 20 years) Several antibiotic treatments for repeated UTI (FQ twice in the last 6 months) Recent weight loss (-35 kg/4 months following slimming cure) current weight 87kg/183 cm Previous surgery : None Current medication : None
The current story started 15 days before admission : anorexia, abdominal pain, deterioration of clinical status and bowel dysfunction without vomiting. The pain got much worse which led to admission. At arrival in the Emergency Department the patient was in major distress AP : 65/40 mm Hg ; HR 142, Temperature 38.9 C Major abdominal pain with rigidity of rectus abdominis Absence of bowel sounds and of bowel movements ( 24 hrs) Signs of peripheral hypoperfusion and acute respiratory failure Orotracheal intubation and mechanical ventilation were performed + Fluid loading (Ringer 1000 ml/10 mn then 1000 ml/30mn) + Epinephrine 0.4 µg/kg/min (2 mg/h) started immediately
Because the patient has an acute abdomen with fever and evidence of bowel obstruction, an exploratory laparotomy was mandatory. A bowel perforation was highly suspected. Due to the severity of the presentation, the medico surgical team decided an immediate laparotomy without additional inquiries.
What is the frequency of severe sepsis in the course of abdominal sepsis? 10 % of the cases admitted in ICU 20% 40% More 8-10 % of all the cases
37% of septic shock among 124 cases of generalized peritonitis (single center study) 3,147 patients enrolled in the SOAP Study (epidemiology of sepsis in 198 ICUs in Europe) 777 (25%) had sepsis on ICU admission 162 (21%) pts abdominal infections 69.8% had severe sepsis 40.1% had septic shock Riche F et al. Crit Care 2009; 13 R99 Volakli E F et al. Crit Care 2010; 14 R32 9% of septic shock among 234 community-acquired cases (25 centers in France) Montravers P et al. J Antimicrob Chemother 2009;63:785-94
Riche F et al. Crit Care 2009; 13 R99
In the course of abdominal sepsis what is the most frequent location of infection? Appendicitis Biliary tract Colon Gastroduodenal All of these locations
Source of infection Roehrborn Krobot Riche Colon 29% 27% 38% Gastroduodenal 28% 22% 22% Small intestine 6% - 18% Biliary tract 7% 7% 8% Appendix 29% 38% 8% Other - 6% 6% Roehrborn A et al. Clin Infect Dis 2001; 33:1513-9 Krobot K et al. Eur J Clin Microbiol Infect Dis 2004 23: 682 7 Riche F et al. Crit Care 2009; 13 R99
Admission parameters Sedation ; Mechanical ventilation FiO2 100% ; Epinephrine 0.4 µg/kg/min (2 mg/h)ekg : sinus tachycardia AP : 95 / 55 ; HR : 125 ; Diuresis : none ph : 7.05 ; PaCO 2 : 38 mm Hg ; PaO 2 : 170 mm Hg ; SaO 2 : 97% ; HCO 3-12 Na : 136 ; K : 4 ; BUN : 10.1 mmol ; Creatinine : 120 µmol Glycemia : 8.3 mmol ; Lactates 6.5 mmol ; Troponin < 0.15 UI/L WBC : 3.39.10 9 /L; Hematocrit : 39% ; Platelets : 198,000.10 9 /L; PT : 73 % ; PTT 36/30
What is the frequency of positive blood cultures in the course of abdominal sepsis? 10 % of the cases admitted in ICU 20% 40% More
Krobot Riche Montravers (Ann Surg 2004) Montravers (JAC 2009) Type of pts CA-IAI Secondary IAI ICU pts Non postoperative IAI CA-IAI (ICU and ward cases) Bacteremia 43% 14% 16% 6% Krobot K et al. Eur J Clin Microbiol Infect Dis 2004 23: 682 7 Riche F et al. Crit Care 2009; 13 R99 Montravers P et al. Ann Surg 2004; 239:409-16 Montravers P et al. J Antimicrob Chemother 2009;63:785-94
Solomkin J et al. Clin Infect Dis 2010;50:133-164
When do you start antibiotic empiric treatment? Immediately in the emergency room After collection of blood cultures At the arrival in the operating room After collection of peritoneal samples Guided by direct examination of peritoneal samples
Solomkin J et al. Clin Infect Dis 2010;50:133-164
PK meropenem in peritonitis Meropenem 1 g / 8 h Intra-abdominal Infections Healthy Volunteers Cmax (mcg/ml) 47.6 17.6 61.6 6.8 AUC (mcg.h/ml) 57.5 20.1 77.5 11.5 T 1/2 (h) 1.04 0.98 Cl (ml/mn) 315 72 188 31 V ss (l) 26.7 6.8 12.5 1.5 Bedikian A. Antimicrob Agents Chemother. 1994;38:151-4.
Crit Care 2010,14:R126
What regimen do you select for antibiotic empiric treatment? Amoxicillin/clavulanic acid Amoxicillin/clavulanic acid + aminoglycosides Piperacillin/tazobactam Ertapenem Imipenem/meropenem/doripenem Cefoxitin Cefotaxime/ceftriaxone + metronidazole Fluoroquinolone + metronidazole (or
Gram positive cocci Gram negative bacilli Anaerobes Streptococci Enterococci Staphylococci Enterobacteriaceae E coli,klebsiella, Enterobacter non fermenting GNB Pseudomonas, Acinetobacter Cocci Streptococci, Peptostreptocci Bacilli Bacteroides, Clostridium,Fusobacterium
% observed 100 75 50 25 0 Bacterial synergy enterobacteriaceae and anaerobes Mortality Abcesses E. coli E. faecalis B. fragilis E. coli + E. faecalis E. coli + B. fragilis E. faecalis + B. fragilis Onderdonk Infect Immun 1976
% 100 75 50 25 0 Mortality Abcesses Contrôle Gentamicine Clindamycine Clindamycine + Gentamicine Weinstein JID 1975
Solomkin J et al. Clin Infect Dis 2010;50:133-164
Solomkin J et al. Clin Infect Dis 2010;50:133-164
Solomkin J et al. Clin Infect Dis 2010;50:133-164
Surgical report: Diffuse stercoral peritonitis Diastatic coecal perforation Obstruction carcinoma of left colon Total colectomy + Ileostomy + Hartmann procedure Peritoneal lavage Peroperative management Heavy fluid loading (5,000 ml of cristalloids) Norepinephrine 2 µg/kg/min (10 mg / h) Antibiotic therapy : Piperacillin/tazobactam + Gentamicin
Admission in ICU in the postoperative period Sedation ; Mechanical ventilation FiO2 100% ; EKG : sinus tachycardia Temp 35 C ; AP : 95 / 55 ; HR : 125 ; Diuresis : none ph : 7.08 ; PaCO 2 : 59 mm Hg ; PaO 2 : 150 mm Hg ; SaO 2 : 92% ; HCO - 3 18 Na : 136 ; K : 4 ; BUN : 6.1 mmol ; Creatinine : 81 µmol Glycemia : 3.3 mmol ; Lactates 2.5 mmol ; Troponin < 0.15 UI/L Bilirubin : 62 mmol ; liver enzymes : Normal value WBC : 21.8.10 9 /L; Hematocrit : 25% ; Platelets : 98,000.10 9 /L; PT : 33 % ; PTT 66/30 APACHE II Score : 28 SAPS II Score : 94 SOFA Score : 15 (Hemo 4, Resp 3, Coagulation 2, Kidney 4, Liver 2) OSF 3 (Cv + Resp + Kidney)
Early management : Sedation Vasopressure support Haemofiltration for acute renal failure and metabolic acidosis Change of empiric antibiotic therapy? Peroperative abdominal samples : Gram negative bacilli (enterobacteriaceae) Gram positive cocci (diplococci) Gram positive bacilli Any additional treatment?
Cruz DN. JAMA 2009;301:2445
Day 1 after surgery Persistent multiple organ failure Sedation Vasopressure support Haemofiltration for acute renal failure and metabolic acidosis Antibiotic therapy Risk of relaparotomy (on demand) in the next coming days
Cultures of peritoneal fluid : E coli, E faecium, Peptostreptococcus magnus, B fragilis AMX AMC TIC TIM PIP PTZ CTX CAZ EPM IMI E coli R R R S S S S S S S E faecium R R R R R R - - - R AMX : amoxicillin ; AMC : amoxicillin + clavulanic acid ; TIC : ticarcillin ; TIM : ticarcillin + clavulanic acid ; PIP : piperacillin ; PTZ: piperacillin + tazobactam; CTX : cefotaxime ; CAZ : Ceftazidime; EPM : Ertapenem; IMI : Imipenem GEN TOB AMK CIP MOXI VAN TEC TIGE LINEZ E coli S S S S S - - S - E faecium Rlo w R R - - S S S S GEN : gentamicin ; TOB : tobramycin ; AMK : amikacin ; CIP : ciprofloxacin ; MOXI: moxifloxacin ; VAN : vancomycin ; TEC: teicoplanin ; TIGE : tigecycline ; LINEZ: linezolide
Etude épidémiologique Bactério-clinique des Infections Intra- Abdominales (EBIIA) Microbiological and clinical epidemiology of intra-abdominal infections 6 months January-June 2005 11 university and 14 non-university hospitals ICU and surgical ward Patients > 18 years Abdominal surgery (open/coelioscopic) for peritonitis with purulent material Microbiological culture of peroperative intra-abdominal samples Montravers P et al. J Antimicrob Chemother 2009;63:785-94
AMC TZP CTX CAZ IPM AMC: amoxicillin/clavulanic acid ; TZP: piperacillin/tazobactam; CTX: cefotaxime; CAZ : ceftazidime ; IPM: imipenem/cilastatin; EPM: Ertapenem EPM Among carbapenems, only imipenem and ertapenem routinely used in France Montravers P et al. J Antimicrob Chemother 2009;63:785-94
AMC TZP CTX CAZ IPM GEN AMK CIP EPM GEN: gentamicin ; AMK: amikacin ; CIP: ciprofloxacin Montravers P et al. J Antimicrob Chemother 2009;63:785-94
AMX: amoxicillin ; EPM: Ertapenem ; GEN: Gentamicin AMX EPM GEN Montravers P et al. J Antimicrob Chemother 2009;63:785-94
AMX: amoxicillin ; EPM: Ertapenem ; GEN: Gentamicin AMX EPM GEN OXA VAN TEC OXA: oxacillin ; VAN: Vancomycin ; TEC: Teicoplanin Montravers P et al. J Antimicrob Chemother 2009;63:785-94
AMX AMC TIC TIM FOX AMX: amoxicillin; AMC: amoxicillin/clavulanic acid ; TIC: Ticarcillin ; TIM: Ticarcillin/clavulanic acid; FOX: cefoxitin Montravers P et al. J Antimicrob Chemother 2009;63:785-94
AMX AMC TIC TIM FOX IPM EPM CLI MTR IPM: imipenem/cilastatin; EPM: Ertapenem; CLI: Clindamycin; MTR: metronidazole Montravers P et al. J Antimicrob Chemother 2009;63:785-94
Early management : Sedation Vasopressure support Haemofiltration for acute renal failure and metabolic acidosis Antibiotic therapy Tigecycline for 10 days
Volakli E F et al. Crit Care 2010; 14 R32
Multivariate analysis 2 failing organs : RR 5.51 CI95%[1.97-15.4] p=0.001 Okubo R. Surg Today 2008;38:413-19
Riche F et al. Crit Care 2009; 13 R99
Multivariate analysis Risk factors of death Presence of yeasts from peritoneal fluid for POP: RR 4.28 CI95%[1.02-18.04] p=0.03 Riche F et al. Crit Care 2009; 13 R99
Riche F et al. Crit Care 2009; 13 R99
Outcome: Progressive improvement over the following 8 days Rapid decrease and interruption of vasoactive drugs Decreased temperature (38 2) and WBC count (15.10 9 /L) Return of diuresis Return of bowel function Weaning from mechanical ventilation at D8 Discharge from ICU at D12 Discharge from hospital at D 16
In summary Early management Source control Importance of adequate antibiotic treatment Limited proof for additional treatments