Low doses of epidural ketamine or neostigmine, but not midazolam, improve morphine analgesia in epidural terminal cancer pain therapy

Lauretti, Gabriela Rocha; Gomes, Jéssica Marcela de Luna; Reis, Marlene Paulino dos; Pereira, Newton Lindolfo

doi:10.1016/s0952-8180(99)00122-1

Cited by 71 publications

(68 citation statements)

References 24 publications

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“…Systematic reviews, consensus conferences, and randomized controlled trials Three systematic reviews [5][6][7], three consensus conferences [8][9][10], and 12 RCTs [11][12][13][14][15][16][17][18][19][20][21][22] met the selection criteria of studies examining clinical effectiveness. Although the systematic reviews and consensus conferences included some relevant RCTs, no single systematic review or consensus conference included all relevant RCTs or sufficiently discussed the effectiveness of intraspinal analgesia for cancer-related pain to support recommendations.…”

Section: Resultsmentioning

confidence: 99%

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Intraspinal techniques for pain management in cancer patients: a systematic review

Myers

Chan

Jarvis

et al. 2009

Support Care Cancer

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Section: Resultsmentioning

confidence: 99%

“…Intraspinal analgesia as an intervention was addressed in a summary of RCTs evaluating adjuvant analgesics. Three of the six RCTs were relevant [17][18][19]. The review concluded insufficient RCT evidence was available to determine the relative efficacy of the spinal versus systemic route of drug administration.…”

Section: Clinical Effectivenessmentioning

confidence: 99%

Intraspinal techniques for pain management in cancer patients: a systematic review

Myers

Chan

Jarvis

et al. 2009

Support Care Cancer

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“…In subanesthetic doses it can also be given as an adjuvant to opiates for the treatment of cancer pain, particularly when opiates alone are ineffective. [35][36][37][38][39][40][41][42] In addition to being a potent NMDA receptor channel blocker, ketamine has other actions, which may contribute to its analgesic and antidepressant effects. These include its interactions with other calcium and sodium channels, cholinergic transmission, noradrenergic and serotonergic reuptake inhibition, glutamate transmission, synapse formation, and l, d, , opioid-like effects.…”

Section: Introductionmentioning

confidence: 99%

Daily Oral Ketamine for the Treatment of Depression and Anxiety in Patients Receiving Hospice Care: A 28-Day Open-Label Proof-of-Concept Trial

Irwin

Iglewicz

Nelesen

et al. 2013

Journal of Palliative Medicine

132

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Background: Depression and anxiety are prevalent and undertreated in patients receiving hospice care. Standard antidepressants do not work rapidly or often enough to benefit most of these patients. Ketamine has many properties that make it an interesting candidate for rapidly treating depression and anxiety in patients receiving hospice care. To test this hypothesis, a 28-day, open-label, proof-of-concept trial of daily oral ketamine administration was conducted in order to evaluate the tolerability, potential efficacy, and time to potential efficacy in treating depression and anxiety in patients receiving hospice care. Methods:In this open-label study, 14 subjects with symptoms of depression or depression mixed with anxiety warranting psychopharmacological intervention received daily oral doses of ketamine hydrochloride (0.5 mg/ kg) over a 28-day period. The primary outcome measure was the Hospital Anxiety and Depression Scale (HADS), which was used to rate overall depression and anxiety symptoms at baseline, and on days 3, 7, 14, 21, and 28. Results: Over the 28-day trial there was significant improvement in both depressive symptoms (F 5,35 = 8.03, p = 0.002, g 2 = 0.534) and symptoms of anxiety (F 5,35 = 14.275, p < 0.001, g 2 = 0.67) for the eight subjects that completed the trial. One hundred percent of subjects completing the trial responded to ketamine for both anxiety and depression. A significant response in depressive symptoms occurred by day 14 for depression (mean D = 3.5, d = 1.14, 95% CI = 1.09-5.9, p = 0.01) and day 3 for anxiety (mean D = 2.4, d = 0.67, 95% CI = 1.0-3.7, p = 0.004). These improvements remained significant through day 28 for both depression (mean D = 4.0, d = 1.34, 95% CI = 2.3-5.9, p = 0.001) and anxiety (mean D = 6.09, d = 1.34, 95% CI = 3.6-8.6, p < 0.001). Side effects were rare, the most common being diarrhea, trouble sleeping, and trouble sitting still. Conclusions: Patients who received daily oral ketamine experienced a robust antidepressant and anxiolytic response with few adverse events. The response rate for depression is similar to those found with IV ketamine; however, the time to response is more protracted. The findings of the potential efficacy of oral ketamine for depression and the response of anxiety symptoms are novel. Further investigation with randomized, controlled clinical trials is necessary to firmly establish the efficacy and safety of oral ketamine for the treatment of depression and anxiety in patients receiving hospice care or other subject populations.

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“…Several adjuvants have been co-administered with bupivacaine, but the results have been either unconvincing or associated with untoward complications [4]. Several researchers have attempted to combine bupivacaine with other anesthetics such as ketamine [5], clonidine [6], midazolam [1], and neostigmine [7] with various success rates.…”

Section: Introductionmentioning

confidence: 99%

“…Neostigmine, a reversible acetylcholinesterase inhibitor, prevents the breakdown of acetylcholine [7]. Lin et al [11] reported that it enhances the release of nitric oxide, suppresses the expression of Fos, and activates muscarinic M2 receptors within the spinal cord.…”

Section: Introductionmentioning

confidence: 99%

Physiological Responses and Gene Expression in Ultrasound-Guided Supraclavicular Brachial Plexus Block: a Comparative Study

Sayyed

Idriss

Gaber

et al. 2018

Cell Physiol Biochem

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Background/Aims: Ultrasound-guided supraclavicular brachial plexus block (BPB) has come into wider use as a regional anesthetic during upper limb operations. This study assessed the neurological and hemodynamic changes and gene expression after co-administration of midazolam or neostigmine with bupivacaine during supraclavicular BPB. Methods: The study involved 90 adults divided into three groups: control (bupivacaine), midazolam (bupivacaine plus midazolam), and neostigmine (bupivacaine plus neostigmine). Blood samples were taken and interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) mRNA levels were measured by real-time PCR, and oxidative stress markers were identified. In addition to the hemodynamic variables, the onset and duration of sensory and motor blockades, duration of analgesia, pain scores, time of first request for an analgesic, and amounts of analgesics ingested were evaluated. Results: Compared with the control and neostigmine groups, the midazolam group experienced longer sensory and motor blockades, prolonged analgesia, lower pain scores at 12 h and 24 h, and lower need for postoperative analgesics. Moreover, the midazolam group exhibited lower oxidative stress markers with a higher fold change in IL-6 and TNF-α mRNA levels. Conclusion: Midazolam co-administered with bupivacaine provided better analgesic quality than did neostigmine with bupivacaine. This might be due to its superior antioxidant and anti-inflammatory effects.

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Low doses of epidural ketamine or neostigmine, but not midazolam, improve morphine analgesia in epidural terminal cancer pain therapy

Cited by 71 publications

References 24 publications

Intraspinal techniques for pain management in cancer patients: a systematic review

Intraspinal techniques for pain management in cancer patients: a systematic review

Daily Oral Ketamine for the Treatment of Depression and Anxiety in Patients Receiving Hospice Care: A 28-Day Open-Label Proof-of-Concept Trial

Physiological Responses and Gene Expression in Ultrasound-Guided Supraclavicular Brachial Plexus Block: a Comparative Study

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