Management of Neutropenic Sepsis Rebecca Frewin Consultant Haematologist Gloucestershire Hospitals NHS Foundation Trust Aims of today What Why How The definition of neutropenic sepsis
Importance for Emergency Clinicians Outcomes of Neutropenic sepsis Assessment of neutropenic sepsis Guidelines for management of neutropenic sepsis Spot diagnoses Definition of Neutropenic Sepsis Diagnose neutropenic sepsis in patients having anticancer treatment whose neutrophil count is 0.5 109 per litre or lower and who have either: a temperature higher than 38oC or other signs or symptoms consistent with clinically
significant sepsis. NICE Clinical Guideline 151: September 2012 Sepsis or Systemic Inflammatory Response Syndrome (SIRS) Patients are often described as being septic or in septic shock Systemic inflammatory response syndrome (SIRS) Temperature >38oC or <36oC Heart rate >90/min Respiratory rate >20 or PaCO2 <4.3kPa White Cell Count >12x 10 9/l Sepsis is defined as SIRS in response to infection Severe sepsis is sepsis associated with:
Organ dysfunction Hypotension (systolic BP <90mmHg or >40mmHg from normal) Organ hypoperfusion (lactic acidosis, oliguria, acute alteration of mental status) Septic shock describes sepsis with hypotension despite adequate fluid resuscitation Deaths from Neutropenic Sepsis 2 deaths/ day from neutropenic sepsis 60% increase in chemotherapy between 2002 2006 More intensive regimes Highest death rate is in 65-79 year olds Neutropenic sepsis: higher risk of dying in
young patients Where do neutropenic sepsis patients present? SACT Report 2008 Approach to neutropenic sepsis 1. Assessment Initial assessment Investigations More detailed review 2. Treatment
Antibiotics Fluid resuscitation Vasopressors Blood product support Initial assessment Brief history Symptoms Recent chemotherapy
Normal neutrophil count Late onset neutropenia in rituximab patients Limited examination MEWs not validated in neutropenic patients Review of any obvious source Investigations For CXR, probability of pneumonia in a child without respiratory symptoms was 1.9% (Phillips et al (2011) Peripheral blood cultures 28/228 cultures were positive (Sheienmann et al (2010). The differential time to positivity of cultures between central and peripheral cultures can be
indicative of catheter related thrombosis NICE Clinical Guideline 151 Early Lactate-Guided Therapy in Intensive Care Unit Patients adjusted HR= 0.61; 95% CI, 0.43-0.87; P= 0.006 Jansen TC. Am J Respir Crit Care Med. 2010;182:752761. Slide 13 Copyright 2014 SCCM/ESICM Treatment: antibiotics
MASCC score in neutropenic sepsis Initial Resuscitation During the first 6 hours, the goals of initial resuscitation of sepsis-induced hypoperfusion should include all of the following as a part of a treatment protocol (Grade 1C): Central venous pressure 8-12 mm Hg Mean arterial pressure 65 mm Hg Urine output 0.5 mL/kg/h Central venous (superior vena cava) or mixed venous oxygen saturation 70% or 65%, respectively
Slide 17 Copyright 2014 SCCM/ESICM Early Goal-Directed Therapy in the Treatment of Severe Sepsis and Septic Shock Control EGDT Relative Risk (95% Confidence Interval)
0.67 (0.46-0.96) 0.03 P Rivers E. N Engl J Med. 2001;345: 1368-1377. Slide 18 Copyright 2014 SCCM/ESICM Fluid Therapy We recommend an initial fluid challenge in patients with sepsis-induced tissue
hypoperfusion with suspicion of hypovolemia to achieve a minimum of 30 mL/kg of crystalloids (a portion of this may be albumin equivalent). More rapid administration and greater amounts of fluid may be needed in some patients. (Grade 1C) Slide 19 Copyright 2014 SCCM/ESICM Fluid Therapy 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 for fluid resuscitation of severe sepsis and septic shock. (Grade 1B) Slide 20 Copyright 2014 SCCM/ESICM Fluid Therapy - Kidney injury Three multicenter randomized trials showed a significant increase in the risk of acute kidney injury with hydroxyethyl starch as compared with crystalloids. Brunkhorst F. N Engl J Med. 2008;358:125-139. Perner A. N Engl J Med. 2012;367:124-134.
Myburgh JA. N Engl J Med. 2012;367:1901-1911. One multicenter randomized trial did not find an increase in the risk of acute kidney injury with hydroxyethyl starch as compared with crystalloids. Guidet B. Crit Care. 2012;16:R94. Slide 21 Copyright 2014 SCCM/ESICM Fluid Therapy We suggest the use of albumin in the fluid
resuscitation of severe sepsis and septic shock when patients require repeated boluses of crystalloids. (Grade 2C) Slide 22 Copyright 2014 SCCM/ESICM Meta-analysis: Albumin versus Other Fluids Outcomes Illustrative comparative risks (95% CI) Assumed Corresponding risk
risk No. Of Quality of the participants evidence (studies) (GRADE) RR 0.84 (0.73 to 0.97) RR 0.85 (0.73 to 0.98)
RR 0.81 (0.57 to 1.16) 1683 (11 studies) moderate Control Short-term mortality Other fluids (may be crystalloid or colloid) Study population
342 per 287 per 1000 1000 (249 to 332) 444 per 377 per 1000 1000 (324 to 440) Relative effect (95% CI) Short-term mortality
(albumin vs crystalloids) Short-term mortality 342 per (albumin vs other 1000 colloids) 1 Grade reduced for imprecision. 195 per 1000 (249 to 396) 1402
Vasopressors Maintain the MAP >65mmHg (Grade 1C) Norepinephrine is recommended as first line vasopressin (Grade 1B) Epinephrine may be added to and potentially substituted for norepinephrine when as additional agent is needed to maintain blood pressure (Grade 2B) Low dose vasopressin (0.03U/min)may be added to norepinephrine with the intent of raising the MAP to target or reducing the norepinephrine dosage Dopamine should be used only as an alternative vasopressor to norepinephrine only in highly selected patients (eg at low risk of arrythmias and/or a low heart rate) (Grade 2C)
Meta-analysis of Norepinephrine versus Dopamine Outcomes Illustrative comparative risks* (95% Relative No. of Quality of the CI) effect participants evidence (95% CI) (studies) (GRADE) Assumed risk Corresponding risk Dopamine
Short-term mortality 482 per 1000 (440 to 524) RR 0.91 2043 (0.83 to (6 studies) 0.99) moderate1,2 82 per 1000
(34 to 195) RR 0.47 1931 (0.38 to (2 studies) 0.58) moderate1,2 15 per 1000 (8 to 27) RR 0.35 1931 (0.19 to (2 studies)
0.66) moderate1,2 Study population 530 per 1000 Serious adverse events Study population Supraventricular arrhythmias 229 per 1000 Serious adverse events Ventricular arrhythmias Norepinephrine
Study population 39 per 1000 *The assumed risk is the median control group risk across studies. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; RR: Risk ratio; Strong heterogeneity in the results (I squared = 85%), however this reflects degree of effect, not direction of effect. We have decided not to lower the evidence quality. 2 Effect results in part from hypovolemic and cardiogenic shock patients in De Backer, NEJM 2010. We have lowered the quality of evidence one level for indirectness. 1 Slide 25
Copyright 2014 SCCM/ESICM Inotropic Therapy We recommend that a trial of dobutamine infusion up to 20 Eg/kg/min be administered or added to vasopressor (if in use) in the presence of: myocardial dysfunction as suggested by elevated cardiac filling pressures and low cardiac output, or ongoing signs of hypoperfusion, despite achieving adequate intravascular volume and adequate mean arterial pressure. (Grade 1C)
We recommend against the use of a strategy to increase cardiac index to predetermined supranormal levels. (Grade 1B) Slide 26 Copyright 2014 SCCM/ESICM Blood product support Maintain Hb >70g/l with a target of 70-90 unless extenuating circumstances such as ischaemic coronary artery disease Give prophylactic platelet transfusions if platelets <10 or <20 with a significant risk of
bleeding. Spot diagnosis in neutropenic patients Spot diagnosis Spot diagnosis Have we covered it all? What Why How
The definition of neutropenic sepsis Importance for Emergency Clinicians Outcomes of Neutropenic sepsis Assessment of neutropenic sepsis Guidelines for management of neutropenic sepsis Spot diagnoses
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