Management of sepsis in neutropenic cancer patients: 2018 guidelines from the Infectious Diseases Working Party (AGIHO) and Intensive Care Working Party (iCHOP) of the German Society of Hematology and Medical Oncology (DGHO)

DGHO-AGIHO · 2019 · Germany

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Authors: Matthias Kochanek, E Schalk, M von Bergwelt-Baildon et al.
Title: Management of sepsis in neutropenic cancer patients: 2018 guidelines from the Infectious Diseases Working Party (AGIHO) and Intensive Care Working Party (iCHOP) of the German Society of Hematology and Medical Oncology (DGHO)
Journal: Annals of Hematology, 2019
DOI: 10.1007/s00277-019-03622-0
Licence: CC BY 4.0
Changes: Verbatim excerpts; formatting adapted

Full text retrieved 2026-10-27 from Europe PMC · PMC6469653

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Recommendations

Verbatim, with grade of recommendation or strength of consensus where given.

Antimicrobial therapy

We recommend initial treatment with piperacillin/tazobactam or meropenem or imipenem/cilastatin (AIII).

Venous thromboembolism prophylaxis

We recommend pharmacologic prophylaxis with unfractionated heparin or low-molecular-weight heparin for venous thromboembolism prophylaxis in the absence of contraindications (AIItr).

Section Initial resuscitation

There is no evidence that sepsis and septic shock in patients with neutropenia need to be treated differently to non-neutropenic patients according to the sepsis guidelines 2016.SoR/QoE: AIII

Section Screening criteria for sepsis and performance improvement

Before admission to the ICU, the treatment goals and the prognosis should be identified. No patients should be admitted to the intensive care unit against their wishes.SoR/QoE: AIII
Patients in neutropenia and signs or symptoms of infection should be screened for sepsis daily.SoR/QoE: AIII
A structured checklist diagnosis is not possible, but the treating physician must decide clinically whether the patient has sepsis.SoR/QoE: AIII
Early warning scoring system and early involvement of intensive care teams on hemato-oncology ward is recommended.SoR/QoE: AIIht
In clinically unclear situations, a neutropenic patient should be admitted early to an ICU. Neutropenia should be used as triage criterion in cancer patients considered for ICU admission.SoR/QoE: AIIr
In critically ill neutropenic cancer patients, ICU admission should not be delayed if indicated.SoR/QoE: AIIt
If a patient has been admitted to the ICU, daily meetings between oncologists and intensivists for care planning and implementation of protocols are recommended.SoR/QoE: AIIt

Section Diagnosis

There is no evidence that sepsis and septic shock in patients with neutropenia differ to non-neutropenic septic patients according to the sepsis guidelines 2016.SoR/QoE: AIII
Neutropenic cancer patients with a suspicion or proof of an infection should be screened for signs of acute organ dysfunction(s) daily.SoR/QoE: AIII
Biomarkers can be used to support the diagnosis of bacterial/fungal infections but are unable to confirm or rule out an infection.SoR/QoE: BIIu-BIII
Modified multiplex PCR protocols might be used to support the diagnosis of an infection leading to sepsis.SoR/QoE: CIIu

Section Antimicrobial therapy

Empirical antimicrobial treatment using anti-pseudomonal broad-spectrum antibiotics must be started immediately in neutropenic patients with sepsis.SoR/QoE: AIIrt
We recommend initial treatment with piperacillin/tazobactam or meropenem or imipenem/cilastatin.SoR/QoE: AIII
A combination treatment with an aminoglycoside may be considered in neutropenic patients with septic shock.SoR/QoE: BIII
In case of clinically stabilizing patients or detection of pathogens sensitive to ß-lactam, it is recommended to stop the aminoglycosides.SoR/QoE: AIII
Risk factors for invasive fungal infections and/or for uncontrolled cardiopulmonary instability, an antifungal therapy should be considered.SoR/QoE: AIII

Section Source control

There is no evidence that source control is different in septic neutropenic patients than non-neutropenic patients according to the sepsis guidelines 2016.SoR/QoE: AIII
A source control (e.g., surgery or CT-controlled puncture) should be done as soon as possible.SoR/QoE: AIIt
If possible, all intravascular devices should be removed in case of suspected infection.SoR/QoE: AIIt

Section Fluid therapy

There is no evidence that septic neutropenic patients need to be treated differently to non-neutropenic patients according to the sepsis guidelines 2016.SoR/QoE: AIII
Balanced crystalloids should be used for intravenous fluid administration.SoR/QoE: AIIt

Section Corticosteroids

There is no evidence that septic shock in patients with neutropenia needs to be treated differently than non-neutropenic patients according to the sepsis guidelines.SoR/QoE: AIII
The continuation of a cortisone therapy should be evaluated individually.SoR/QoE: AIII

Section Blood products

There is no evidence that sepsis and septic shock in patients with neutropenia require different treatment than non-neutropenic patients according to the sepsis guidelines 2016.SoR/QoE: AIII
Red blood cell (RBC) transfusion: we recommend that RBC transfusion occurs only when hemoglobin concentration decreases to < 7.0 g/dL (4.3 mmol/L) in adults in the absence of particular circumstances, such as myocardial ischemia, severe hypoxemia, or acute hemorrhage. No RBC transfusions should be performed for hemoglobin concentrations ≥ 7 g/dL (4.3 mmol/L) in the absence of risk factors.SoR/QoE: DIIt
Granulocytes transfusion: there is low-grade evidence that patients do not benefit from therapeutic granulocyte transfusions in terms of clinical resolution of infection.SoR/QoE: CIII
Platelet transfusion: in the absence of other risk factors for bleeding prophylactic, platelet transfusions should be given using the standard trigger level (≤ 10 × 109/L).SoR/QoE: BI-IItr
For neutropenic septic patients or prior to an intervention with an increased risk of bleeding, platelet transfusions should be indicated individually.SoR/QoE: AIII

Section Hematopoietic growth factors

We do not recommend the routine additional use of G-CSF or GM-CSF to standard treatment of sepsis and septic shock in patients with neutropenia.SoR/QoE: DI-IIr
G-CSF–induced neutropenia recovery carries a risk of respiratory status deterioration with acute lung injury or ARDS.SoR/QoE: DIII

Section Immunoglobulins

There is marginally degree of evidence to support the use of intravenous immunoglobulins (IVIG) in sepsis and septic shock in patients with neutropenia.SoR/QoE: CIIrt

Section Blood purification

Cytokine adsorption cannot be recommended at this time for sepsis and septic shock in patients with neutropenia.SoR/QoE: DIIt-III

Section Anticoagulants

There are no studies supporting the use of heparin in sepsis and septic shock in patients with neutropenia.SoR/QoE: DIII
There is insufficient evidence to support antithrombin substitution in any category of critically ill participants including the subset of patients with sepsis and disseminated intravascular coagulation.SoR/QoE: DIItr

Section Mechanical ventilation

NIV should not be used in patients with a respiratory failure and a PaO2/FiO2 lower than 150 mmHg.SoR/QoE: DIIt
NIV did not improve survival compared to oxygen only.SoR/QoE: AIIrt
High-flow nasal cannula (HFNC) oxygen when compared with standard oxygen did not reduce intubation or survival rates and may be used in special circumstances.SoR/QoE: AIIt
Prone position is recommended for patients with severe ARDS.SoR/QoE: BIItr

Section Sedation and analgesia

There is no evidence that sepsis and septic shock in patients with neutropenia need to be treated differently than non-neutropenic patients according to the sepsis guidelines 2016.SoR/QoE: AIII
A strategy for whole-body physiotherapy—consisting of interruption of sedation and physical and occupational therapy in the earliest days of critical illness—is recommended.SoR/QoE: AIII
The use of standardized weaning protocols is recommended.SoR/QoE: AIItr

Section Bicarbonate therapy

There is no evidence that septic shock in patients with neutropenia needs to be treated differently than non-neutropenic patients according to the sepsis guidelines 2016.SoR/QoE: AIII

Section Venous thromboembolism prophylaxis

We recommend pharmacologic prophylaxis with unfractionated heparin or low-molecular-weight heparin for venous thromboembolism prophylaxis in the absence of contraindications.SoR/QoE: AIItr

Section Stress ulcer prophylaxis

There is no evidence that sepsis and septic shock in patients with neutropenia need to be treated differently than non-neutropenic patients.SoR/QoE: AIII

Section Nutrition

In patients with severe neutropenic enterocolitis, severe viral or bacterial gastrointestinal infections, or severe gastrointestinal graft-versus-host disease (GVHD), enteral nutrition should be paused or, at least, carried out with caution.SoR/QoE: AIII
Concomitant cancer-associated cachexia should not result in hyperalimentation.SoR/QoE: AIII
Enteral nutrition is preferred over parenteral nutrition, because it is associated with a lower rate of infections.SoR/QoE: BIIt

Section Setting goals of care

Treatment goals and the short- and long-term prognosis of intensive care should be discussed with the patient and the relatives before admission to the intensive care unit.SoR/QoE: AIII
Full-code ICU management (without limitations of ICU resources) should be offered to all critical ill cancer patients if long-term survival may be compatible with the general prognosis of the underlying malignancy.SoR/QoE: AIIu
Immediately after admission to intensive care, we recommend discussing care and prognosis goals with patients and families.SoR/QoE: AIII
There should be a daily exchange between intensive care physician and oncologists.SoR/QoE: AIII
Therapy goals and prognosis must be re-evaluated daily and communicated to the relatives.SoR/QoE: AIII
Possibilities for a better comprehension and therapy goal finding should be offered to the intensive care team and/or relatives. This includes printed information, structured communication, palliative care consultation, ethics consultation, or the use of structured family conferences conducted by the usual ICU team.SoR/QoE: BIII
At any time point, all issues discussed must be communicated throughout the whole intensive care team. Differences in therapy goals should be recognized and discussed in the team.SoR/QoE: AIII

Abstract

Sepsis and septic shock are major causes of mortality during chemotherapy-induced neutropenia for malignancies requiring urgent treatment. Thus, awareness of the presenting characteristics and prompt management is most important. Improved management of sepsis during neutropenia may reduce the mortality of cancer therapies. However, optimal management may differ between neutropenic and non-neutropenic patients. The aim of the current guideline is to give evidence-based recommendations for hematologists, oncologists, and intensive care physicians on how to manage adult patients with neutropenia and sepsis.

Contents of the original publication

The section headings of the original.

Introduction
Pathophysiology
Definition
Incidence/proportion
Risk factors associated with neutropenic sepsis
Factors for bacteremia/infection
Factors for development of sepsis and septic shock
Initial resuscitation
Screening criteria for sepsis and performance improvement
Diagnosis
Antimicrobial therapy
Source control
Fluid therapy
Vasoactive medications
Corticosteroids
Blood products
Hematopoietic growth factors
Immunoglobulins
Blood purification
Anticoagulants
Mechanical ventilation
Sedation, analgesia, and physiotherapeutic prophylaxis
Glucose control
Management of renal dysfunction—renal replacement therapy
Bicarbonate therapy
Venous thromboembolism prophylaxis
Stress ulcer prophylaxis
Nutrition
Setting goals of care
Compliance with ethical standards

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