Opioid treatment of pain is generally safe with 0.5% or less events from respiratory depression. However, fatalities are regularly reported. The only treatment currently available to reverse opioid respiratory depression is by naloxone infusion. The efficacy of naloxone depends on its own pharmacological characteristics and on those (including receptor kinetics) of the opioid that needs reversal. Short elimination of naloxone and biophase equilibration half-lives and rapid receptor kinetics complicates reversal of high-affinity opioids. An opioid with high receptor affinity will require greater naloxone concentrations and/or a continuous infusion before reversal sets in compared with an opioid with lower receptor affinity. The clinical approach to severe opioid-induced respiratory depression is to titrate naloxone to effect and continue treatment by continuous infusion until chances for renarcotization have diminished. New approaches to prevent opioid respiratory depression without affecting analgesia have led to the experimental application of serotinine agonists, ampakines, and the antibiotic minocycline.

/pdf/incidence-reversal-and-prevention-of-opioid-induced-334b3xe51f.pdf

Incidence, Reversal, and Prevention of Opioid-induced Respiratory Depression.

Normal levels of trace elements in human blood plasma or serum

Lethal hyperkalemic response to succinylcholine continues to be reported, but the molecular mechanisms for the hyperkalemia have not been completely elucidated. In the normal innervated mature muscle, the acetylcholine receptors (AChRs) are located only in the junctional area. In certain pathologic states, including upper or lower motor denervation, chemical denervation by muscle relaxants, drugs, or toxins, immobilization, infection, direct muscle trauma, muscle tumor, or muscle inflammation, and/or burn injury, there is up-regulation (increase) of AChRs spreading throughout the muscle membrane, with the additional expression of two new isoforms of AChRs. The depolarization of these AChRs that are spread throughout the muscle membrane by succinylcholine and its metabolites leads to potassium efflux from the muscle, leading to hyperkalemia. The nicotinic (neuronal) 7 acetylcholine receptors, recently described to be expressed in muscle also, can be depolarized not only by acetylcholine and succinylcholine but also by choline, persistently, and possibly play a critical role in the hyperkalemic response to succinylcholine in patients with upregulated AChRs.

/pdf/succinylcholine-induced-hyperkalemia-in-acquired-pathologic-br4ggkudtc.pdf

Succinylcholine-induced hyperkalemia in acquired pathologic states: etiologic factors and molecular mechanisms.

Objective: To determine whether endogenous opioids contribute to the pruritus of cholestasis by studying the effect of the opiate antagonist naloxone on the perception of pruritus and on scratching...

Effects of naloxone infusions in patients with the pruritus of cholestasis. A double-blind, randomized, controlled trial

https://www.gastrojournal.org/article/0016-5085(92)90102-5/pdf

A controlled trial of naloxone infusions for the pruritus of chronic cholestasis

Massive hyperkalemia after administration of succinylcholine.

Six hours after intravenous injection of morphine, 2 mg/kg, seven healthy adults received a ten-hour intravenous infusion of naloxone (3.66 μg/kg loading dose plus 3.66 μg/kg/hr), totaling 40 μg/kg. Immediately before administration of naloxone, resting minute ventilation (E) was 6.2 ± 0.4 (SE) l/mi

Reversal of morphine anesthesia with naloxone.

The effects of two levels of morphine-nitrous oxide anesthesia on cerebral blood flow (CBF) and cerebral metabolism (CMRO2) were measured in healthy male volunteers. CBF and metabolic measurements were made in the awake control state, after morphine, 1 mg/kg, with 70 per cent nitrous oxide and 30 per cent oxygen, and at a total dose of 3 mg/kg morphine with the same concentrations of nitrous oxide and oxygen. Ventilation was controlled and carbon dioxide added to inspired gas to maintain PaCO2 constant at 40 torr. CBF was 48.2 +/- 4.4 (SEM) ml/100 g/min during the control phase; 45.7 +/- 6.4 ml/100 g/min after 1 mg/kg morphine, and 44.3 +/- 4.9 ml/100 g/min after 3 mg/kg morphine. The latter values are not significantly different from control. Cerebral metabolic rates for oxygen, glucose, and lactate were normal in the control phase and did not change significantly when morphine was present at either level. It is concluded that morphine-nitrous oxide anesthesia produces no alteration of cerebral blood flow or metabolism in normal man at the two dose levels studies.

Cerebral blood flow and metabolism during morphine--nitrous oxide anesthesia in man.

Seven healthy male volunteers received 6.6 plus or minus 0.5 (SE) per cent-hours of halothane-oxygen anesthesia without surgery. Serum bromide concentrations increased from 0.6 plus or minus 0.1 before anesthesia to 2.9 plus or minus 0.2 mEq/l on the second day after anesthesia. On the ninth day serum bromide was still elevated to 2.5 plus or minus 0.1 mEq/l. These bromide concentrations represent psychoactive levels and may account for previously recognized prolonged changes in mood and intellectual function after halothane. Plasma and urinary fluoride concentrations did not increase significantly.

Increased Serum Bromide Concentration after Halothane Anesthesia in Man

The magnitude of errors due to spectral overlap and collsion broadening by nitrous oxide in the infrared analysis of carbon dioxide were separately determined in a group of Godart Capnographs. Errors caused by spectral overlap ranged from 0.08 to 0.7 per cent apparent CO2 when 70 per cent N2O was analyzed. These were sufficiently variable to necessitate determination by each investigator for his own equipment. Errors resulting from collision broadening were lees than 0.5 per cent apparent CO2 when 5 per cent CO2 was analyzed with 70 per cent N2O as the background gas. These errors were not sufficiently variable to necessitate individual determination. Machine age was not significantly correlates with the magnitude of error due to either effect.

Eric M. Kennell

Papers

Massive hyperkalemia after administration of succinylcholine.

Reversal of morphine anesthesia with naloxone.

Cerebral blood flow and metabolism during morphine--nitrous oxide anesthesia in man.

Increased Serum Bromide Concentration after Halothane Anesthesia in Man

Correction Factors for Nitrous Oxide in the Infrared Analysis of Carbon Dioxide