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Open Access 01-12-2022 | Care | Study protocol

The “Blood pressure and oxygenation targets in post resuscitation care, a randomized clinical trial”: design and statistical analysis plan

Authors: Jesper Kjaergaard, Henrik Schmidt, Jacob E. Møller, Christian Hassager

Published in: Trials | Issue 1/2022

Abstract

Background

Comatose patients admitted after resuscitation from cardiac arrest have a significant risk of poor outcome due to hypoxic brain injury. While numerous studies have investigated and challenged the target temperature as the efficacious part of the guideline endorsed Targeted Temperature Management (TTM) protocols, our knowledge and how the remaining parts of the TTM are optimized remain sparse. The present randomized trial investigated two aspects of the TTM protocol: target blood pressure during the ICU stay and oxygenation during mechanical ventilation. Furthermore, the efficacy of device-based post-TTM fever management is addressed.

Methods

Investigator-initiated, dual-center, randomized clinical trial in comatose OHCA patients admitted to an intensive cardiac care unit. Patients are eligible for inclusion if unconscious, older than 18 years of age, and have return of spontaneous circulation for more than 20 min.

Intervention: allocation 1:1:1:1 into a group defined by (a) blood pressure targets in double-blind intervention targeting a mean arterial blood pressure of 63 or 77 mmHg and (b) restrictive (9–10 kPa) or liberal (13–14 kPa) of arterial oxygen concentration during mechanical ventilation. As a subordinate intervention, device-based active fever management is discontinued after 36 h or 72. Patients will otherwise receive protocolized standard of care according to international guidelines, including targeted temperature management at 36 °C for 24 h, sedation with fentanyl and propofol, and multimodal neuro-prognostication. Primary endpoint: Discharge from hospital in poor neurological status (Cerebral Performance category 3 or 4) or death, whichever comes first. Secondary outcomes: Time to initiation of renal replacement therapy or death, neuron-specific enolase (NSE) level at 48 h, MOCA score at day 90, Modified Ranking Scale (mRS) and CPC at 3 months, NT-pro-BNP at 90 days, eGFR and LVEF at 90 days, daily cumulated vasopressor requirement during ICU stay, and need for a combination of vasopressors and inotropic agents or mechanical circulatory support.

Discussion

We hypothesize that low or high target blood pressure and restrictive and liberal oxygen administration will have an impact on mortality by reducing the risk and degree of hypoxic brain injury. This will be assessment neurological outcome and biochemical and neuropsychological testing after 90 days.

Trial registration

ClinicalTrials.gov NCT03141099. Registered on May 2017 (retrospectively registered)

Sepsis: Infection is the inflammatory response to the presence of microorganisms or the invasion of normally sterile host tissue by those organisms.

The Systemic Inflammatory Response Syndrome (SIRS) is diagnosed when the patient exhibits two of the following four abnormalities:

Temperature > 38 °C or < 36 °C
Heart rate > 90 beats min⁻¹
Respiratory rate > 20 breaths min⁻¹ or PaCO2 < 4.3 kPa or need for mechanical ventilation
White blood cell count > 12,000 cells mm⁻³ or < 4000 cells mm⁻³ or > 10% immature cells (band forms)

Sepsis is SIRS resulting from infection. Severe sepsis is sepsis associated with organ dysfunction, hypoperfusion or hypotension. Hypoperfusion and perfusion abnormalities may include, but are not limited to, lactic acidosis, oliguria, or an acute alteration in mental status.

Septic shock is sepsis with hypotension (systolic blood pressure < 90 mmHg or a reduction of > 40 mmHg frombaseline) and perfusion abnormalities (see severe sepsis above) or the requirement for vasoactive drugs despite adequate fluid resuscitation in the absence of other causes for hypotension.

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Title: The “Blood pressure and oxygenation targets in post resuscitation care, a randomized clinical trial”: design and statistical analysis plan
Authors: Jesper Kjaergaard
Henrik Schmidt
Jacob E. Møller
Christian Hassager
Publication date: 01-12-2022
Publisher: BioMed Central
Keywords: Care
Temperature Management
Published in: Trials / Issue 1/2022
Electronic ISSN: 1745-6215
DOI: https://doi.org/10.1186/s13063-022-06101-6

Keynote webinar | Spotlight on medication adherence

Springer Medicine

The “Blood pressure and oxygenation targets in post resuscitation care, a randomized clinical trial”: design and statistical analysis plan

Abstract

Background

Methods

Discussion

Trial registration

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Discussion

Trial registration

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