The Role of a Low-Dose Ketamine-Midazolam Regimen in the Management of Severe Painful Crisis in Patients With Sickle Cell Disease

Tawfic, Qutaiba A.; Faris, Ali S.; Kausalya, Rajini

doi:10.1016/j.jpainsymman.2013.03.012

Cited by 48 publications

(37 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, 1,014 of these studies were excluded (Fig 1). Among the eligible 20 studies, 3 systematic reviews, 9 non-RCTs [19–27] and 2 RCTs [28,29] were excluded: a case series and a letter [19,26], three retrospective studies [23–25], studies that used treatments other than intravenous infusion [20,21,23], a prospective study in which both ketamine and hydromorphine were simultaneously used without a control group [22], and another study that was a prospective cohort study with multiple biases, such as selection, performance, detection, and reporting bias [27]. None of the above excluded studies were RCTs.…”

Section: Resultsmentioning

confidence: 99%

The Effects of Low-Dose Ketamine on Acute Pain in an Emergency Setting: A Systematic Review and Meta-Analysis

Lee

2016

PLoS ONE

View full text Add to dashboard Cite

ObjectivesCurrently ketamine is not used often as an analgesic in the emergency department (ED). Nonetheless, it can increase the efficiency of opioids and decrease their side effects. The purpose of this systematic review and meta-analysis was to evaluate whether low-dose ketamine in the ED provides better analgesia with fewer adverse effects.MethodsThe PubMed, EMBASE, and Cochrane Library databases were searched by two reviewers independently (last search performed on January 2016). Data were also extracted independently.ResultsA total of 6 trials involving 438 patients were included in the current analysis. Our subgroup analysis of pain reduction indicates that the favorable effects of ketamine were similar or superior to those of placebo or opioids, although these effects were heterogeneous. However, low-dose ketamine was associated with a higher risk of neurological (relative risk [RR] = 2.17, 95% confidence interval [CI] = 1.37–3.42, P < 0.001) and psychological events (RR = 13.86, 95% CI = 4.85–39.58, P < 0.001). In contrast, the opioid group had a higher risk of major cardiopulmonary events (RR = 0.22, 95% CI = 0.05–1.01, P = 0.05).ConclusionsThe efficiency of ketamine varies depending on the pain site, but low-dose ketamine may be a key agent for pain control in the ED, as it has no side effects. It may also help to reduce the side effects of opioids.

show abstract

Section: Resultsmentioning

confidence: 99%

The Effects of Low-Dose Ketamine on Acute Pain in an Emergency Setting: A Systematic Review and Meta-Analysis

Lee

2016

PLoS ONE

View full text Add to dashboard Cite

show abstract

“…The Hargreaves’ test was performed to evaluate the response to acute thermal stimulation (Tawfic et al, 2014). We used a mobile radiant heat-emitting device with an aperture of 10 mm in diameter (37370-Plantar Test, Ugo Basile, Italy) to produce acute noxious thermal stimuli and measure the latency to paw withdrawal.…”

Section: Methodsmentioning

confidence: 99%

Corticostriatal Regulation of Acute Pain

Martinez

Lin

Zhou

et al. 2017

Front. Cell. Neurosci.

View full text Add to dashboard Cite

The mechanisms for acute pain regulation in the brain are not well understood. The prefrontal cortex (PFC) provides top-down control of emotional processes, and it projects to the nucleus accumbens (NAc). This corticostriatal projection forms an important regulatory pathway within the brain’s reward system. Recently, this projection has been suggested to control both sensory and affective phenotypes specifically associated with chronic pain. As this projection is also known to play a role in the transition from acute to chronic pain, we hypothesized that this corticostriatal circuit can also exert a modulatory function in the acute pain state. Here, we used optogenetics to specifically target the projection from the PFC to the NAc. We tested sensory pain behaviors with Hargreaves’ test and mechanical allodynia, and aversive pain behaviors with conditioned place preference (CPP) test. We found that the activation of this corticostriatal circuit gave rise to bilateral relief from peripheral nociceptive inputs. Activation of this circuit also provided important control for the aversive response to transient noxious stimulations. Hence, our results support a novel role for corticostriatal circuitry in acute pain regulation.

show abstract

“…Management of pain due to the activation of the NMDA receptor includes efforts to close it or prevent its activation. Medications that may close the NMDA receptor, at least partially, include opioid rotation, ketamine , methadone , lidocaine, and other local anesthetics as reported by a few case reports and anecdotes. Methadone is a racemic compound with dextro‐ and levo‐isomers ( dl ‐methadone).…”

Section: Intractable Vocs With Persistent Pain In Between Episodesmentioning

confidence: 99%

Pathophysiology and principles of management of the many faces of the acute vaso‐occlusive crisis in patients with sickle cell disease

Ballas

2014

European J of Haematology

View full text Add to dashboard Cite

Effective management of sickle cell pain entails a thorough understanding of its pathophysiology and the pharmacogenomics of the opioids used to manage it. In recent years, there has been significant progress along these two lines. At the pathophysiologic level, there is evidence that the severity and frequency of painful stimuli modulate their transmission at the level of the dorsal horn of the spinal cord. This modulation is achieved via two channels: the a-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and NMDA receptors. Initially, the AMPA channel controls the transmission of stimuli of mild-moderate severity. Once the AMPA channel reaches its limit of membrane depolarization, the NMDA channel is activated and facilitates the transmission of painful stimuli in a progressive fashion leading to central sensitization and glial activation. At the level of pharmacogenomics, the metabolism of each opioid is patient-specific. Glucuronidation is unique for the metabolism of morphine, hydromorphone, and oxymorphone. The metabolism of all other opioids requires specific Cytochrome P450 (CYP) isoenzymes. The activity of each isoenzyme and the activity of the metabolites of each opioid vary among patients depending on their genetic makeup and coexistent environmental factors such as the use of other medications that may enhance or inhibit the CYP isoenzyme activity. The clinical picture of sickle cell disease (SCD) in general and sickle cell anemia (SS) in particular has evolved significantly over the years. In the 1950s, 1960s, and 1970s, many patients died during childhood or young adulthood (1-3) and the knowledge of healthcare providers about sickle cell pain and its management were suboptimal. Since then, things have improved significantly but not totally. With the advent of newborn screening, penicillin/antibiotic prophylaxis, better vaccines, better antibiotics, safer blood transfusion, iron chelation therapy and hydroxyurea survival and the quality of life of patients with SCD improved (4, 5), and it is not unusual nowadays to have occasional patients with SCD who are 50-70 yr old. With increased longevity, however, a host of new phenomena appeared and the incidence of new complications of SCD became apparent and previously milder complications became more severe and more common. The acute vaso-occlusive crisis (VOC), for example, is no more characterized by the intermittent sudden onset and sudden offset only with pain-free periods in between recurrent VOCs; chronic pain syndromes have become more common and more severe requiring special treatments and interventions, neuropathic pain has been well documented in transgenic sickle cell mice, and most importantly numerous comorbidities emerged that complicate the already complex disease. There are at least 23 comorbid conditions reported in SCD (6). Despite these advances, management of acute sickle cell pain did not change much; it is still fixed at the level of type, amount, frequency, and

show abstract

The Role of a Low-Dose Ketamine-Midazolam Regimen in the Management of Severe Painful Crisis in Patients With Sickle Cell Disease

Abstract: Low-dose ketamine-midazolam IV infusion might be effective in reducing pain and opioid requirements in patients with sickle cell disease with severe painful crisis. Further controlled studies are required to prove this effect.

Cited by 48 publications

References 23 publications

The Effects of Low-Dose Ketamine on Acute Pain in an Emergency Setting: A Systematic Review and Meta-Analysis

The Effects of Low-Dose Ketamine on Acute Pain in an Emergency Setting: A Systematic Review and Meta-Analysis

Corticostriatal Regulation of Acute Pain

Pathophysiology and principles of management of the many faces of the acute vaso‐occlusive crisis in patients with sickle cell disease

Contact Info

Product

Resources

About