Influence of Morphine or Ketamine or Saline Applied During In-hospital Cardiopulmonary Resuscitation on Early Survival

NCT04009759 | Unknown Phase 1

• 1 other identifier: Akershus university hospital
• Study Type: interventional
• Target: 240
• Locations: 0 countries
• Sites: N/A

Brief Summary

A small numbers of patients (10-15%) treated with cardiopulmonary resuscitation (CPR) are discharged from hospitals with a favorable neurologic outcome. However, a higher incidence of chest injuries (30-70%), mainly rib and sternum fractures, are observed among the survivors. It's no surprise that 6 months after cardiac arrest (CA) 50-70% of the patients who have survived continue to have pain and stress-related problems. Based on the need for the pain/stress treatment in these patients and several experimental evidences demonstrating neuroprotective features of anesthetics it is logical to presume that application of anesthesia during CPR may be indicated. In rodents exposed to hypoxic gas (5% 02, 95% N2) for 70 min, all seven animals died at the end of the experiments in the naloxone pre-treated group while only one out of seven rats died in the morphine pre-treated group, and five of seven rats died in the control group. In human volunteers, intravenously administered 60 mg of morphine did not alter cerebral blood flow and cerebral vascular resistance but markedly depressed cerebral oxygen uptake. Interestingly, in critical patients, morphine even in low doses is effective in relieving dyspnea by altering central perception and decreasing anxiety. In rats, morphine demonstrates dose- depending reduction of cerebral glucose utilization in limbic and forebrain regions. Thus, the main points of application for morphine in treatment of CA may be a reduction of oxygen/glucose consumption. Pre-treatment of zebrafish with ketamine protects against cardiac arrest-induced brain injury by inhibiting Ca2+ wave propagation and consequently it improves survival rate. Inhibition of NMDA receptors by ketamine reduces neuronal apoptosis and attenuates the systemic inflammatory response to tissue injury. The sympathomimetic effects of ketamine may facilitates recovery of systemic blood pressure during CPR. Retrospective investigations demonstrate that patients who are treated with opioids before or during CA have a statistically significantly higher survival rate and much better neurological outcome compared to untreated patients. Experimental studies have a limitation as all animals are treated with anesthesia and therefore survival rate varies between 50-90%. Thus, prospective research is urgently needed to investigate the influence of morphine or/and ketamine on survival and neurological outcome in patients with CA.

Conditions

Cardiac Arrest

Keywords

cardiac arrest; Morphine; Ketamine; Survival rate

Outcome Measures

Primary Outcomes (1)

• Survival at 28 days in patients after in-hospital cardiac arrest

  Survival rate at 28 days in patients after in-hospital cardiac arrest treated or not with Morphine or ketamine during CPR

  28th day

Secondary Outcomes (6)

• Measurement of biochemical markers of brain damage (NSE, S-100B protein)

  2,12, 24 and 48 hours

• Length of stay in the intensive care unit

  3 month

• Length of stay in the hospital

  3 months

• Survival rate at 3 months after cardiac arrest

  3 months

• Neurological outcome at the hospital discharge

  6 months

Study Arms (3)

Morphine

ACTIVE COMPARATOR

Morphine group (M) (n=80), where patients will be treated with i.v. injection of Morphine 2 mg/ml - 5 ml - 10 mg "Epidural". The treatment will be given during CPR as soon as possible.

Drug: Morphine

Ketamine

ACTIVE COMPARATOR

Ketamine (K) group (n=80), where patients will be treated with i.v. injection of S-Ketamine 10 mg/ml - 5 ml - 50 mg "Ketamin Abcur". The treatment will be given during CPR as soon as possible.

Drug: Ketamine Injectable Solution

Saline

PLACEBO COMPARATOR

Control group (n=80), where patients will be treated with i.v. 5 ml of NaCl 0,9% "B. Braun". The treatment will be given during CPR as soon as possible.

Drug: Saline 0.9%

Interventions

Morphine DRUG

Adult patients with an in-hospital cardiac arrest will be evaluated by anaesthesiologists for inclusions criteria to the study and randomised to get the blinded study medicine as addition to standard treatment of cardiac arrest. Randomization will be performed by means of sealed envelopes containing number of syringe that will be used.

Morphine

Ketamine Injectable Solution DRUG

Adult patients with an in-hospital cardiac arrest will be evaluated by anaesthesiologists for inclusions criteria to the study and randomised to get the blinded study medicine as addition to standard treatment of cardiac arrest. Randomization will be performed by means of sealed envelopes containing number of syringe that will be used.

Also known as: Ketamine

Ketamine

Saline 0.9% DRUG

Adult patients with an in-hospital cardiac arrest will be evaluated by anaesthesiologists for inclusions criteria to the study and randomised to get the blinded study medicine as addition to standard treatment of cardiac arrest. Randomization will be performed by means of sealed envelopes containing number of syringe that will be used.

Also known as: Saline

Saline

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \- All adult patients with in-hospital cardiac arrest

You may not qualify if:

• an age of less than 18 years
• drugs poisoning or the administration of opioids or Ketamine 24 hours before the cardiac arrest
• terminal phase of oncological or other chronic diseases
• poor communication and physical capabilities due to psychiatric or neurological diseases
• dementia or Alzheimers
• extremely reduced weight or physical ability and activity
• known history of chronic use of opioids/Ketamine

Sponsors & Collaborators

• University Hospital, Akershus: lead

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Related Links

• Related Info

MeSH Terms

Conditions

Heart Arrest

Interventions

Morphine; Ketamine; Sodium Chloride

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Morphine Derivatives; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Central Study Contacts

Vladimir Kuklin, dr med

CONTACT

+4798838024; vkuklin@me.com

Lisa Dybvik, cand med

CONTACT

+4746669271; ldybvik@hotmail.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Acute bag for cardiopulmonary resuscitation (CPR) will have a trial pack containing 3 blinded ampules that will be labelled with only randomisation number. Anaesthesiologists and nurses performing CPR and research treatment will not know the content of the ampules as well as a meaning of the randomisation number. Neurologist, who will not be aware of treatment assignments, will assess neurological outcomes in all survived patients. Statistician, who will not be aware of treatment assignments, will assess statistical data in all included patients. An independent Data Monitoring Committee will assess the progress, safety data (death, long-term hospitalization, and disability) and, critical efficacy endpoints of the clinical study (survival at 1, 2, 3 and 28 days in patients after in-hospital CA) in all included patients.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of day case surgery unit

Model Details: 240 adult patients with an in-hospital cardiac arrest will be evaluated by anesthesiologist on duty for inclusions criteria to the study and randomized to get the blinded study medicine as addition to the standard treatment of cardiac arrest.

Study Record Dates

• First Submitted: February 16, 2019
• First Posted: July 5, 2019
• Study Start: October 1, 2021
• Primary Completion: January 1, 2025
• Study Completion: January 1, 2026
• Last Updated: June 11, 2021

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will not share