Cholangitis and Early Goal Directed Therapy

EM-CCM CONFERENCE SUMMARY

PRESENTED BY DR. PIA DANIEL

SUMMARY BY DR. FRANCIS YOUN

CASE: Elderly, bedbound, nonverbal female with past history of dementia, hypothyroidism, sigmoid volvulus s/p sigmoidectomy and colostomy sent from NH for altered mental status, fever, and concern for bowel obstruction.

VS: T 103, BP 99/60, HR 125, RR 28, SpO2 88%, FS 91

PRIMARY ASSESSMENT: protecting airway, clear and bilateral breath sounds, tachypneic, hypoxic, tachycardic.

INITIAL INTERVENTIONS: IV/O2/monitor, 2L NS bolus, PR acetaminophen, foley catheterization

SECONDARY ASSESSMENT (notable findings): decreased responsiveness, dry mucous membranes, tachycardia, clear lung sounds, RUQ tenderness to palpation, no rashes or decubiti, no LE edema, moving all extremities, moans to pain

WORKING DIAGNOSIS: SIRS, presumed sepsis (UTI, colitis, diverticulitis, cholecystitis, cholangitis, pancreatitis, pneumonia, meningitis), bowel obstruction, intracranial mass/lesion/hemorrhage

FURTHER INTERVENTIONS: Broad-spectrum antibiotics (vancomycin, piperacillin/tazobactam), subclavian central venous catheter placement, norepinephrine vasopressor infusion, IV fluid boluses

LABS (notable): pH 7.3, lactate 5.4, CO2 20, Cr 1.5, WBC 6.19, AST 180, ALT 200, Alk Phos 585, Tbili 6.6, Dbili 4.6, Lipase 1,000

ECG: sinus tachycardia

CXR: no focal consolidation, unchanged from previous

CT abdomen/pelvis: choledocholithiasis (multiple with largest 7mm), intra- and extra-hepatic bile duct obstruction, CBD 15mm, CBD sludge, normal pancreas

HOSPITAL COURSE:

Additional abx added (gentamicin and metronidazole), general surgery consulted, GI consulted

Admit to SICU; emergent ERCP with stone extraction and stent placement as well as laparoscopic repair of perforated duodenum

FINAL ASSESSMENT: Septic shock secondary to acute cholangitis with biliary obstruction and duodenal perforation

DISCUSSION:

CHOLANGITIS: biliary tract infection (primary etiologies: CBD stones or medical interventions)

– Charcot’s Triad: fever, jaundice, RUQ pain

– Reynold’s Pentad: fever, jaundice, RUQ pain, shock, and AMS

– MGMT: U/S, CT, antibiotics, endoscopic biliary drainage and decompression via ERCP or PTC imaging modalities or if GI unsuccessful, surgical management comprises decompression of the biliary tree, including stone extraction, T-tube insertion, transhepatic intubation of bile duct or bilio-enteric bypass, or as an alternative, percutaneous transhepatic biliary drainage (PTBD)

SEPSIS:

– Definitions:

– SIRS: 2 or more of the following: T < 36.0 or > 38.0, HR > 90, RR > 20 or pCO2 < 32, WBC < 4,000 or > 12,000 or > 10% bands

– SEPSIS: SIRS + source of infection

– SEVERE SEPSIS: SEPSIS + evidence of end-organ dysfunction (in the ED, end-organ dysfunction cannot be immediately assessed, so lactate > 4 is used)

– SEPTIC SHOCK: SEVERE SEPSIS and hypotension (despite initial fluid resuscitation – 30cc/kg)

– Causes:

– Gram(+): S. aureus, S. pneumonia

– Gram(-): E. coli, Klebsiella, Pseudomonas

– Empiric Antimicrobial Treatment (IDSA)

– CAP: ceftriaxone + azithromycin OR resp quinolone

– CAP (High-risk): cefepime + cipro OR zosyn + cipro OR meropenem + cipro

– Intra-abdominal: metronidazole PLUS ceftriaxone OR cefepime OR quinolone; alternative: piperacillin-tazobactam

– UTI: ceftriaxone OR ciprofloxacin OR cefepime

– Unknown: vancomycin PLUS zosyn OR cefepime OR meropenem OR moxifloxacin

– Early Goal-Directed Therapy (EGDT) Management: Rivers (NEJM, 2001)

– EGDT = aggressive hemodynamic management and monitoring

– Goals: CVP 8-12, ScvO2 > 70%, MAP > 65

– 60-day mortality 50% for EGDT vs. 70% for ST (standard therapy)

– 2012 Surviving Sepsis Campaign Guidelines (variations from EGDT)

– use of alternative markers: procalcitonin (inflammatory marker but poor test characteristics), lactate (tissue perfusion marker); goals based on time windows

– Within first 3 hours for severe sepsis: crystalloid bolus 30cc/kg in 30 min using pressure bag, antibiotics within first hour of recognition, ≥2 blood cultures, source identification and control, serial lactate

– 2006 Crit Care Med: abx within 1^st hour survival rate = 79%; each hour delay = 7.6% decrease in survival rate [“the clock starts ticking when the diagnosis of severe sepsis is made”, i.e. if lactate > 4, consider likely source when choosing antibiotics, but cover broadly if source remains unclear; if lactate is < 4, you have time to possibly IDENTIFY source prior to antibiosis]

– Within first 6 hours: CVP 6-12, MAP > 65, UOP > 0.5cc/kg/hr, ScvO2 > 70, downtrending lactate

– Chest 2008: poor correlation between CVP and fluid status

– AJEM 2012: maximal IVC diameter less in hypovolemic vs. euvolemic pts

– 2014 J US Med: IVC collapse > 40% is associated with fluid responsiveness

– Intensive Care Med 2005: MAP < 65% independently associated with increased mortality

– NEJM 2014: MAP 80-85 vs. MAP 65-70 showed no significant difference in mortality at 28 and 90 days

– JAMA 2010: lactate clearance of 10% noninferior to ScvO2 > 70% with respect to in-hospital mortality

– Crit Care Med 2004: 11% decreased mortality benefit for each 10% in lactate clearance

– Additional Guidelines:

– Vasopressor: norepinephrine is 1^st-line, then epinephrine

– Inotrope: Dobutamine

– Hydrocortisone: only if patient is hypotensive despite IVF/pressors

– Blood transfusion: hgb < 7

ProCESS: Protocolized Care for Early Septic Shock: EGDT vs. Protocolized Standard Care (SC) vs. SC alone (MD discretion); primary endpoint is survival (60d, 90d, 1yr)

– Group 1: EGDT: Tight hemodynamic monitoring, CVC, 6 hour time frame

– Group 2: Protocolized SC: Tight monitoring, no CVC required, 6 hr time frame

– Group 3: SC: no guidelines

– RESULTS: Prior to randomization, all groups 2L NS bolus, 75% rec’d abx; EGDT = 21% mortality, Protocolized SC = 18% mortality, SC = 18.9% mortality

CONCLUSION: no difference in outcomes between groups, decreased emphasis on invasive monitoring; although ScvO2 has been de-emphasized, one may use it to decide on RBC transfusion – If hct is low, but not quite < 21 and ScvO2 is <70%, then consider transfusion

REFERENCES:

Dellinger RP, Levy MM, Rhodes A, et al. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med. 2013;41(2):580-637.
Dipti A, Soucy Z, Surana A, et al. Role of inferior vena cava diameter in assessment of volume status: a meta-analysis. AJEM. 2012;30:1414-1419
Jones AE, Shapiro NI, Trzeciak S, et al. Lactate clearance vs central venous oxygen saturation as goals of early sepsis therapy: a randomized clinical trial. JAMA. 2010;303(8):739-746
Marik PE, Baram M, Vahid B. Does central venous pressure predict fluid responsiveness? Asystematic review of the literature and the tale of seven mares. Chest. 2008; 134 (): 172-1785.
Marik PE, Cavallazzi R, Vasu T, et al. Dynamic changes in arterial waveform derived variables and fluid responsiveness in mechanically ventilated patients: a systematic review of the literature. Crit Care Med. 2009;37:2642-2647
Rivers E, Nguyen B, Havstad S, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001;345:1368-1377
Shapiro et al. A Randomized Trial of Protocol-Based Care for Early Septic Shock. N Engl J Med 2014; 370:1683-1693
Varpula M, Tallgren M, Saukkonen K, et al. Hemodynamic variables related to outcome in septic shock. Intensive Care Med. 2005 Aug;31(8):1066-71