Managing Patients with Sepsis Diagnosis; Initial Resuscitation; ARRT Initiation Prof. Achim Jörres, M.D. Dept. of Nephrology and Medical Intensive Care Charité University Hospital Campus Virchow Klinikum Berlin, Germany achim.joerres@charite.de
Male Patient, Age 43 Years During last 2-3 days feeling moderately unwell with signs of upper respiratory tract infection (cough), but mobile and going out of the house until yesterday morning. Yesterday feeling increasingly unwell with mounting weakness and dyspnea. Towards the evening increasingly confused with slurred speech, weakness; unable to walk; spouse called emergency services. Admitted to emergency room: Temperature 38.9 C; HR 110/min, BP 110/70 mmhg; CRP 12 mg/dl, rales on auscultation; chest X-ray with suspected pneumonia. Antibiotic therapy (piperacillin/combactam), admission to ward. Next morning development of hypotension, dyspnea/tachypnea and O 2 desaturation (80%) transfer to ICU
Vital parameters following ICU admission Temperature 40.6 C O 2 saturation 87% Heart rate 150/min Respiratory rate 26/min BP syst. 90 mmhg BP diast. 50 mmhg Urine output
Labs Metabolic acidosis with respiratory compensation AKI Inflammation Liver enzymes Rhabdomyolysis Anemia Thrombopenia DIC
Sepsis A Disease Continuum Infection SIRS Sepsis Severe Sepsis At least 2 symptoms: Temp >38 C or < 36 C Heart rate > 90/min Respiratory rate > 20/min WBC > 11,500 oder < 4,000 or > 10% neutrophils SIRS with suspected or proven infectious origin Sepsis + organ dysfunction Circulation SHOCK! Kidney Lung BPsys <90 mmhg Liver MAD <65 mmhg Needs vasopressors Coagulation despite 20-40 ml/kg CNS fluid resuscitation
SURVIVING SEPSIS CAMPAIGN CARE BUNDLES TO BE COMPLETED WITHIN 3 HOURS: 1) Measure lactate level 2) Obtain blood cultures prior to administration of antibiotics 3) Administer broad spectrum antibiotics 4) Administer 30 ml/kg crystalloid for hypotension or lactate 4 mmol/l Dellinger R et al. Critical Care Med. 2013; 41: 580-637
Initial resuscitation (first 6 hours): Begin resuscitation immediately in patients with hypotension or elevated serum lactate >4 mmol/l; do not delay pending ICU admission. Resuscitation goals: Central venous pressure (CVP) 8 12 mm Hg Mean arterial pressure 65 mm Hg Urine output 0.5 ml kg -1 hr -1 Central venous (superior vena cava) oxygen saturation 70%, or mixed venous 65% 11-2014 Dellinger R et al. Critical Care Med. 2013; 41: 580-637
Prospective RCT in 263 patients with severe sepsis / septic shock upon hospital admission, six hours of early goal-directed therapy vs. standard therapy before admission to ICU In-hospital mortality was 30.5% in the group with early goal-directed therapy, vs. 46.5% with standard therapy (P=0.009). Rivers E et al, NEJM 2001; 345:1368-77
Total fluid administered over 72 h was not different between the groups, however: During the first 6 hours patients with early goaldirected therapy received significantly more fluid infusion early golden hours Rivers E et al, NEJM 2001; 345:1368-77
Prospective RCT, 1600 patients in 51 centers (mostly in Australia or New Zealand) presenting to the emergency department with early septic shock were randomized to EGDT vs. usual care Primary outcome was all-cause mortality within 90 days NEJM 2014; 371: 1496-506
Prospective RCT, 1600 patients in 51 centers (mostly in Australia or New Zealand) presenting to the emergency department with early septic shock were randomized to EGDT vs. usual care Primary outcome was all-cause mortality within 90 days NEJM 2014; 371: 1496-506
Prospective RCT, 1600 patients in 51 centers (mostly in Australia or New Zealand) presenting to the emergency department with early septic shock were randomized to EGDT vs. usual care Primary outcome was all-cause mortality within 90 days NEJM 2014; 371: 1496-506
Prospective RCT, 1341 patients in 31 U.S. centers presenting to the emergency department with septic shock were randomized to EGDT vs. protocol-based standard therapy (no CVC placement, administration of inotropes, or blood transfusions) vs. usual care Primary outcome was in-hospital mortality within 60 days NEJM 2014; 370: 1683-1693
NEJM 2014; 370: 1683-1693
Surviving Sepsis Campaign Statement Regarding Hemodynamic and Oximetric Monitoring in Response to ProCESS and ARISE Trials (October 1, 2014) Required monitoring of CVP and ScvO 2 via a CVC as part of an early resuscitation strategy does not confer survival benefit in all patients with septic shock who have received timely antibiotics and fluid resuscitation compared with controls. Requiring measurement of CVP and ScvO 2 in all patients who have lactate results >4 mmol/l and/or persistent hypotension after initial fluid challenge and who have received timely antibiotics is not supported by the available scientific evidence. The results of the ProCESS and ARISE trials have not demonstrated any adverse outcomes in the groups that utilized CVP and ScvO 2 as end points for resuscitation. Therefore, no harm exists in keeping the current SSC bundles intact until a thorough appraisal of all available data has been performed. http://www.survivingsepsis.org/
Excessive Fluid Resuscitation Clinical consequences Impaired pulmonary function Impaired mental status Bowel dysfunction Intra-abdominal compartment syndrome Myocardial dysfunction Increased risk of decubital ulcers Delayed wound healing Muscle weakness / impaired mobilisation
Prospective observational study; 618 critically ill patients with AKI (5 UScentres) With RRT Fluid overload (>10% over baseline) independently associated with mortality but kidney function and renal recovery not improved Without RRT Bouchard et al., Kidney Int. 2009; 76: 422-7
Fluid Resuscitation Early interventions to achieve hemodynamic stability in patients with septic shock may reduce mortality Rapid fluid resuscitation of central importance Excessive fluid resuscitation and overhydration may lead to increased mortality and worse renal recovery
Crystalloids or Colloids?
Prospective, randomised study; 6,997 ICU patients in Australia and New Zealand Comparison of fluid resuscitation with 4% albumin vs. saline (28 days) 726 deaths in the albumin group, 729 deaths in the saline group (RR 0.99; 95 % CI, 0.91-1.09; P=0.87). No difference regarding: ICU days (6.5 ± 6.6 with albumin vs. 6.2 ± 6.2 with saline, P=0.44) Hospital days (15.3 ± 9.6 vs. 15.6+/-9.6, P=0.30) Days on mechanical ventilation (4.5 ± 6.1 and 4.3 ± 5.7, P=0.74) Days on RRT (0.5 ± 2.3 and 0.4 ± 2.0, P=0.41). Finfer et al, N. Engl. J. Med. 2004; 350: 2247-56.
(CHEST) Crystalloid versus Hydroxyethyl Starch Trial 7,000 ICU patients (43% surgical) in AU/NZ randomised to FR with HES 130/0.4 (max. 50 ml/kg/day) or Saline 0.9% No difference in survival More patients in HES group required ARRT Myburgh et al, NEJM 2012; 367(20):1901-11
Meta-analysis of 38 randomized controlled trials Hydroxyethyl starch was found to be associated with increased mortality among 10,290 patients (RR 1.09; 95% CI 1.02-1.17) increased renal failure among 8,725 patients (RR, 1.27; 95% CI 1.09-1.47) and increased use of renal replacement therapy among 9,258 patients (RR, 1.32; 95% CI, 1.15 to 1.50) Zarychanski R et al, JAMA 2013; 309 (7):678-688
Fluid Therapy of Severe Sepsis We recommend crystalloids be used as the initial fluid of choice in the resuscitation of severe sepsis and septic shock (grade 1B). We recommend against the use of hydroxyethyl starches (HES) for fluid resuscitation of severe sepsis and septic shock (grade 1B). We suggest the use of albumin in the fluid resuscitation of severe sepsis and septic shock when patients require substantial amounts of crystalloids (grade 2C). 11-2014 Dellinger R et al. Critical Care Med. 2013; 41: 580-637
AKI Guideline 3.1. Hemodynamic monitoring and support for prevention and management of AKI 1. In the absence of hemorrhagic shock, we suggest using isotonic crystalloids rather than colloids (albumin or starches) as initial management for expansion of intravascular volume in patients at risk for AKI or with AKI. (2B) 2. We recommend the use of vasopressors in conjunction with fluids in patients with vasomotor shock with, or at risk for, AKI. (1C) 3. We suggest using protocol-based management of hemodynamic and oxygenation parameters to prevent development or worsening of AKI in high-risk patients in the perioperative setting (2C) or in patients with septic shock (2C). Kidney Int. Suppl. Volume 2, No 1 (March 2012)
When to initiate acute dialysis?
When to initiate acute dialysis? Generally accepted indications Refractory hyperkalaemia (>6.5 mmol/l) Refractory volume overload Refractory metabolic acidosis (ph 7.1) Uraemic organ complications (e.g. pericarditis) Timely start: Serum urea concentration? Serum creatinine? AKI Stage?????
Most studies favour early start of RRT Paucity of randomized controlled trials, use of variable definitions of early RRT, and publication bias preclude definitive conclusions Seabra et al., AJKD 2008; 52: 272-84
Most studies favour early start of RRT The overall design and quality of studies comparing early versus late initiation of RRT in critically ill patients with AKI is low. Earlier initiation of RRT in critically ill patients with AKI may have a beneficial impact on survival Karvellas et al., Crit. Care 2011; 15: R72
Sepsis/Multiorgan Failure Should we start pre-emptive RRT?
Prospective multicenter RCT in 80 patients with sepsis/septic shock (study inclusion within 24h after first organ failure) CVVH for 96h with 25 ml/kg h vs. standard medical therapy Study stopped following Interim analysis! CVVH group: Higher number and severity of organ failure More/prolonged AKI (need for CVVH >96h) No reduction of plasma cytokines Payen D. et al., Crit. Care Med. 2009; 37: 803-10
Substudy of the FINNAKI (Finnish Acute Kidney Injury) study conducted in 2011-2012 in 17 ICUs with 2901 patients Patients were classified as pre-emptive (no conventional indications) and classic (one or more indications) RRT recipients. Patients with classic RRT were further divided into classic-urgent (RRT initiated 12 hours from manifesting indications) and classic-delayed (RRT>12 hours from first indication). Additionally, 2450 patients treated without RRT were matched to patients with preemptive RRT. Of 239 patients treated with RRT, 134 fulfilled at least one conventional indication before commencing RRT. Vaara et al, CJASN 2014; 9: 1577-85
Vaara et al, CJASN 2014; 9: 1577-85
Patients on RRT after one or more conventional indications had higher crude and adjusted 90-day mortality compared with patients without conventional indications. Highest mortality in group with delayed RRT (>24 h) and classic indications Vaara et al, CJASN 2014; 9: 1577-85
Timing of Acute Renal Replacement Therapy 1. Initiate RRT emergently when life-threatening changes in fluid, electrolyte, and acid-base balance exist. (Not Graded) 2. Consider the broader clinical context, the presence of conditions that can be modified with RRT, and trends of laboratory tests rather than single BUN and creatinine thresholds alone when making the decision to start RRT. (Not Graded) ARRT should be initiated once AKI is established and unavoidable but before overt complications have developed. The threshold for initiating RRT should be lowered when AKI occurs as part of multi-organ failure. The initiation of RRT may be deferred if the underlying clinical condition is improving and there are early signs of renal recovery. British Renal Association Standards Jörres A et al., Nephrol. Dial. Transplant. 2013; 28: 2940-5 KDIGO Group, Kidney Int. Suppl. Vol.2, No 1 (March 2012)
Acute Renal Replacement Therapy in Patients with AKI as Part of Multiorgan Failure Check for acute RRT indications Restore fluid status and circulation, correct electrolyte abnormalities Treat underlying problems If oliguria persists despite adequate fluid resuscitation and hemodynamic management, consider to start RRT without further delay (i.e. within 12-24 hours) Prefer CRRT (or extended dialysis) over classic ihd Prescribe adequate RRT dose (e.g., 30 ml/kg/h in CRRT) in order to achieve the minimum recommended dose (20-25 ml/kg/h)