Topics

Ketamine for Acute Painful Crisis in Sickle Cell Disease Patients

2018-02-18 18:36:19 | BioPortfolio

Summary

We hypothesize that administration of ketamine for pain relief in sickle cell patients with vaso-occlusive crisis early on will lead to a more rapid improvement in pain score and less narcotic requirement.

Description

Sickle cell disease is an inherited hematological disorder where the shape of red blood cells is altered into a sickle-like cells resulting in red blood cell destruction and therefore anemia and other complications. It's a widely spread condition in African American population as well as the Southern and Eastern Provinces of Arabian Peninsula.

Acute painful episodes are a very common complication of the disease process, mainly thought to be a result of tissue ischemia due to occlusion of the microcirculation with clusters of sickled RBC(1). This usually involves long bones or spine but can involve other areas. Acute painful crises can also be precipitated by cold exposure, dehydration, infection, hypoxia, acidosis or hypercarbia, or in some cases it is not related to a specific trigger. This condition puts the patient in severe pain requiring multiple Emergency Department (ED) visits and sometimes admission to the hospital. Currently the mainstay of therapy for acute painful crises is hydration and IV analgesia (2). This makes pain control challenging for the emergency physician as management of acute painful crises requires multiple doses of IV opioids, a retrospective study of 19 patients and 57 visits showed that accumulative dose of IV morphine ranged between 4 mg and 26.7 (0.05-0.5 mg/kg) during 70% of the visits. 50% of the patients were admitted after less than 3 hours of ED treatment, 28% of the discharged patients returned to the ED within 3 days (3). Moreover, as other chronic pain patients, sickle cell disease patients develop opioid induced hyperalgesia (OIH) leading to activation of N- methyl D Aspartate receptors (NMDA) (1).

The use of ketamine, a non-competitive NMDA receptor antagonist, may have the potential to modulate the OIH through impaired sensitization of spinal neurons to nociceptive stimuli and may, therefore, impede development of and blunt neuropathic pain. Extensive search of the literature database showed few published reports and retrospective studies including few patients which have addressed the use of low-dose ketamine in the management of acute painful crises in SCD (4-6). A retrospective study (5) included 5 children and adolescents received a low-dose ketamine infusion for the treatment of sickle cell-related pain demonstrated reduced pain scores in 40% of patients and significant reduction in opioid utilization in only 20% of patients. However, that report was retrospective, non-powered, and included few patients. A recent Canadian retrospective study including 9 adult and adolescent patients demonstrated statistically significant reduced cumulative morphine consumption (146±16.5 mg/day vs. 112.±12.2 mg/day) and pain scores after adding intravenous ketamine in patients with painful sickle cell crises (7). Similarly, another American investigators reported decreased opioid consumption with infusing low-dose ketamine as an adjuvant analgesic in 30 patients presented with sickle cell disease with VOC, that study was retrospective (2). Moreover, in year 2017, a prospective, randomized, double dummy trial was done comparing the adverse effects and analgesic efficacy of low-dose ketamine for acute pain in the ED either by single intravenous push or short infusion. This study shows that low-dose ketamine administered as short infusion is related with a significantly lower rates of feeling of unreality and sedation with no difference in analgesic efficacy in comparison to intravenous push (8)

To the best of our knowledge, there is no a large, prospective, comparative, controlled clinical trial investigated the addition of low-dose ketamine in shortening the ER stays and improving the quality of analgesia in patients with VOC.

Sample Size

A data obtained from a pilot study included 10 patients received either morphine or ketamine showed that the mean and SD of pain VAS at 1-hour following administering the study drug among patients presented with sickle-cell VOC were (Morphine 6.5 ± 3.41565, Ketamine: 1.6667 ± 1.52753).

An a priori power analysis indicated that a sample size of 220 patients is sufficiently large to detect a mean difference in the pain VAS of 1.5 that would have a clinical importance, with a type-I error of 0.05 and a power of 90%. Additional patients (20%) will be added for a final sample size of 264 patients to compensate for those dropping out during the study.

Interim Analysis

An independent safety committee will perform three interim analyses on information time 25% (55 patients), 50% (110 patients) and 75% (165 patients). Data evaluation at each interim analysis will be based on the alpha spending function concept, according to Lan and DeMets, and will employ O'Brien-Fleming Z-test boundaries, which are very conservative early in the trial. For the first interim analysis the efficacy stopping rule would require an extremely low P value (P< 0.000015). For the second interim analysis P< 0.003 will be taken as efficacy stopping rule. For the third interim analysis P< 0.02 will be taken as efficacy stopping rule. Investigators will be kept blind to the interim analysis results.

Study Design

Conditions

Sickle Cell Crisis

Intervention

Control Group, Ketamine Group, standard IV hydration, Rescue Morphine

Location

Imam Abdulrahman Bin Faisal University
Dammam
Eastern
Saudi Arabia
31952

Status

Recruiting

Source

Dammam University

Results (where available)

View Results

Links

Published on BioPortfolio: 2018-02-18T18:36:19-0500

Clinical Trials [9724 Associated Clinical Trials listed on BioPortfolio]

Comparison of Oral Morphine Versus Nasal Ketamine Spray With Chitosan in Cancer Pain Outpatients

34 adult (>18 years) cancer pain outpatients with Opioid base therapy because of pain and breakthrough pain or extreme pain on movement will be included in this prospective, randomized, do...

Ketamine Associated With Morphine PCA After Total Hip Arthroplasty

Ketamine (an analgesic drug often associated with morphine in the treatment of Opioid Induced Hyperalgesia) is often mixed in Morphine PCA syringe. We make the hypothesis that ketamine adm...

Pain Medicine for Wound Care Procedures

This is a randomized double-blind study to determine if the administration of a small-dose of ketamine (an anesthetic)added to morphine (an opioid) contributes to reducing pain intensity d...

Morphine or/and Ketamine in Out-of-hospital Cardiac Arrest

Preclinical studies demonstrate that opioids can preserve cellular integrity status during acute hypoxia in many organs and tissues including: intestine, skeletal muscle, myocardium and br...

The Use of Ketamine as Rescue Analgesia in the Recovery Room Following Opioid Administration. A Double-Blind Randomised Trial in Postoperative Patients

This clinical trial will determine if postoperative patients who have postoperative pain, which has been refractory to morphine administration, will have improved pain relief following a b...

PubMed Articles [22506 Associated PubMed Articles listed on BioPortfolio]

Intermittent administration of low dose ketamine can shorten the course of electroconvulsive therapy for depression and reduce complications: A randomized controlled trial.

This study aimed to investigate the efficacy and safety of intermittent low-dose ketamine on improving the efficacy of ECT. Patients diagnosed with Major Depressive Disorder (MDD) (n = 134) were r...

OPIATES IN THE COMPLEX OF ANALGESIA AFTER THORACOTOMY AND ANALYSIS OF THE COMPLICATIONS.

The goal: to study the influence of various methods of analgesia on the state of postoperative anesthesia in patients after thoracotomy; compare the quantity of narcotic analgesics (morphine) used in ...

Addition of magnesium sulfate to intraperitoneal ropivacaine for perioperative analgesia in canine ovariohysterectomy.

Magnesium may be used as an adjunctive analgesic for perioperative pain management because of its antinociceptive properties. This study investigated the analgesic efficacy of intraperitoneal ropivaca...

Pharmacokinetics of an intravenous constant rate infusion of a morphine-lidocaine-ketamine combination in Holstein calves undergoing umbilical herniorrhaphy.

To describe the pharmacokinetics of morphine, lidocaine, and ketamine associated with IV administration of a constant rate infusion (CRI) of a morphine-lidocaine-ketamine (MLK) combination to calves u...

H3K4 dimethylation at FosB promoter in the striatum of chronic stressed rats promotes morphine-induced conditioned place preference.

Expression of FosB gene in striatum is essential in addiction establishment. Activated glucocorticoid receptors (GRs) induce FosB gene expression in response to stressor. Therefore, elevation of FosB ...

Medical and Biotech [MESH] Definitions

Groups that serve as a standard for comparison in experimental studies. They are similar in relevant characteristics to the experimental group but do not receive the experimental intervention.

A cyclohexanone derivative used for induction of anesthesia. Its mechanism of action is not well understood, but ketamine can block NMDA receptors (RECEPTORS, N-METHYL-D-ASPARTATE) and may interact with sigma receptors.

A study in which observations are made before and after an intervention, both in a group that receives the intervention and in a control group that does not.

Studies which start with the identification of persons with a disease of interest and a control (comparison, referent) group without the disease. The relationship of an attribute to the disease is examined by comparing diseased and non-diseased persons with regard to the frequency or levels of the attribute in each group.

Activities devoted to freeing persons or animals from danger to life or well-being in accidents, fires, bombings, floods, earthquakes, other disasters and life-threatening conditions. While usually performed by team efforts, rescue work is not restricted to organized services.

More From BioPortfolio on "Ketamine for Acute Painful Crisis in Sickle Cell Disease Patients"

Quick Search

Relevant Topics

Pain
Pain is defined by the International Association for the Study of Pain as “an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage”. Some illnesses can be excruci...

Pain Disorder
Pain is a feeling (sharp or dull) triggered in the nervous system which can be transient or constant. Pain can be specific to one area of the body eg back, abdomen or chest or more general all over the body eg muscles ache from the flu. Without pain ...


Searches Linking to this Trial