Chemical Compatibility of Regional Anesthetic Drug Combinations

Christie, Joan M.; Jones, Clifton W.; Markowsky, Susan J.

doi:10.1177/106002809202600904

Cited by 12 publications

(9 citation statements)

References 3 publications

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“…While comprehensive data on the physicochemical compatibility of all potential admixtures are lacking, existing evidence is supportive. Lidocaine is stable when mixed with morphine or fentanyl [28]. Bupivacaine is compatible with hydromorphone [29], morphine and fentanyl [28, 30].…”

Section: Resultsmentioning

confidence: 99%

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Pharmacological and clinical implications of local anaesthetic mixtures: a narrative review

Nestor

Sepúlveda

et al. 2021

Anaesthesia

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Summary Various techniques have been explored to prolong the duration and improve the efficacy of local anaesthetic nerve blocks. Some of these involve mixing local anaesthetics or adding adjuncts. We did a literature review of studies published between 01 May 2011 and 01 May 2021 that studied specific combinations of local anaesthetics and adjuncts. The rationale behind mixing long‐ and short‐acting local anaesthetics to hasten onset and extend duration is flawed on pharmacokinetic principles. Most local anaesthetic adjuncts are not licensed for use in this manner and the consequences of untested admixtures and adjuncts range from making the solution ineffective to potential harm. Pharmaceutical compatibility needs to be established before administration. The compatibility of drugs from the same class cannot be inferred and each admixture requires individual review. Precipitation on mixing (steroids, non‐steroidal anti‐inflammatory drugs) and subsequent embolisation can lead to serious adverse events, although these are rare. The additive itself or its preservative can have neurotoxic (adrenaline, midazolam) and/or chondrotoxic properties (non‐steroidal anti‐inflammatory drugs). The prolongation of block may occur at the expense of motor block quality (ketamine) or block onset (magnesium). Adverse effects for some adjuncts appear to be dose‐dependent and recommendations concerning optimal dosing are lacking. An important confounding factor is whether studies used systemic administration of the adjunct as a control to accurately identify an additional benefit of perineural administration. The challenge of how best to prolong block duration while minimising adverse events remains a topic of interest with further research required.

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Section: Resultsmentioning

confidence: 99%

“…Lidocaine is stable when mixed with morphine or fentanyl [28]. Bupivacaine is compatible with hydromorphone [29], morphine and fentanyl [28, 30]. Levobupivacaine combined with fentanyl also remains stable [31].…”

Section: Resultsmentioning

confidence: 99%

Pharmacological and clinical implications of local anaesthetic mixtures: a narrative review

Nestor

Sepúlveda

et al. 2021

Anaesthesia

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“…The solution remained clear and colorless. Christie and colleagues 20 reported the stability of a similar three-component admixture. Specifically, preservative-free injectable solutions of each component were added to produce a final admixture containing morphine sulfate (0.2 mg/mL), bupivacaine HCl (1.5 mg/mL) and clonidine HCl (30 g/mL) that was stored in polypropylene syringes for 1 hour at room temperature.…”

Section: Discussionmentioning

confidence: 99%

Stability and Compatibility of Morphine-Clonidine Admixtures in an Implantable Infusion System

Hildebrand

Elsberry

Hassenbusch

2003

Journal of Pain and Symptom Management

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Nonopioid analgesics are often coadministered with intrathecal morphine to increase efficacy. The purpose of this study was to evaluate stability and compatibility of morphine-clonidine admixtures with an implantable infusion system that is commonly used to treat pain patients. Infusion systems were filled with admixture and maintained at 37 degrees C for 90 days. Samples were collected monthly. Drug concentrations were determined using stability-indicating, high-performance liquid chromatography. For compatibility testing, individual materials comprising the fluid pathway of the device were immersed in clonidine solution and stored at 37 degrees C for various periods through 64 weeks and mechanical performance evaluated. After 3 months of containment in the infusion system, morphine and clonidine concentrations remained at > or = 94% of the theoretical starting concentrations. All device materials retained acceptable mechanical performance following clonidine exposure. These results demonstrate that morphine and clonidine are stable when combined in aqueous solution maintained at body temperature in an implantable infusion system for at least 3 months.

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“…To establish the synergic or additive effect of the combinations used in epidural or subarachnoid applications, the physical–chemical compatibility of the drugs must be known. Christie et al. (1992) assessed the effects of morphine, fentanil, bupivacaine, LD, tetracaine, ketamine and CL administered in different combinations, and demonstrated the physical and chemical compatibility of these agents can be observed in vitro .…”

Section: Introductionmentioning

confidence: 99%

Clinical evaluation of clonidine added to lidocaine solution for subarachnoid analgesia in sheep

DeRossi

Righetto

Almeida

et al. 2006

Vet Pharm & Therapeutics

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Clonidine (CL) is a alpha2-adrenergic agonist that produces analgesia in animals and humans by a non-opiate alpha2-adrenergic action in the spinal cord dorsal horn. The objective of this prospective randomized study was to investigate the clinical effects of CL/lidocaine (LD) combination administered by the subarachnoid route in sheep. Each sheep received each of three treatments, at no shorter than weekly intervals. Treatments consisted of 0.003 mg/kg CL, 1.2 mg/kg LD and a combination of CL (0.003 mg/kg) and LD (1.2 mg/kg) (CLLD). Subarachnoid injections were given in all animals between the last lumbar and first sacral vertebra. Heart rate (HR), arterial pressures, respiratory rate, rectal temperature, analgesia, sedation, and motor blockade were determined before drug administration (basal) and 5, 10, 15 and 30 min after drug administration, and at 30-min intervals until loss of analgesia occurred. The duration of analgesia after subarachnoid CLLD administration was 187 +/- 24 min (mean +/- SD), i.e. more than twice of that obtained with CL (99 +/- 19 min) or LD (55 +/- 4.4 min) alone. In all sheep, CL, administered either alone or with LD, induced moderate sedation. After subarachnoid administration of three treatments, all sheep had ataxia and subsequent sternal recumbency. The CL treatment causes decreases in blood pressure (diastolic arterial pressure and mean arterial pressure) and HR. Data suggest that the CLLD combination could be used subarachnoidally in sheep requiring prolonged surgery.

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Chemical Compatibility of Regional Anesthetic Drug Combinations

Abstract: The agents evaluated demonstrated physical and chemical compatibility under conditions that would be observed during the administration of peridural anesthesia. Combinations of these drugs therefore could be safely admixed for use in anesthesia.

Cited by 12 publications

References 3 publications

Pharmacological and clinical implications of local anaesthetic mixtures: a narrative review

Pharmacological and clinical implications of local anaesthetic mixtures: a narrative review

Stability and Compatibility of Morphine-Clonidine Admixtures in an Implantable Infusion System

Clinical evaluation of clonidine added to lidocaine solution for subarachnoid analgesia in sheep

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