Respiratory depression with opioids

Ketamine may be ideal to treat post-operative pain after adenotonsillectomy. It avoids the feared risks of bleeding with NSAIDs and respiratory depression with opioids. Ketamine at a dose of 0.5 mg/kg IV reduces post-operative pain and need for other analgesics. Peritonsillar infiltration at the same dose has a similar effect to the intravenous dose. The time of administration either before the start or the conclusion of surgery has no bearing on the analgesic effect. If prolonged pain is anticipated a ketamine infusion of 0.3 6 mg/kg per h can be started after the administration of a loading dose of 0.5 mg/kg. 

Sarton E, Teppema L, Dahan A (2008) Naloxone reversal of opioid-induced respiratory depression with special emphasis on the partial agonist/antagonist buprenorphine. Adv Exp Med Biol 605 486 91... 

The principal effects of opioid analgesics with affinity for n- receptors are on the CNS the more important ones include analgesia, euphoria, sedation, and respiratory depression. With repeated use, a high degree of tolerance occurs to all of these effects (Table 31-3). 

Only six of 36 children who took overdoses of co-phenotrope had signs of atropine overdose (central nervous system excitement, hypertension, fever, flushed dry skin) (1). Opioid overdose (central nervous system and respiratory depression with miosis) predominated or occurred without any signs of atropine toxicity in 33 cases (92%). Diphenoxylate-induced hjrpoxia was the major problem and was associated with slow or fast respiration, hypotonia or rigidity, cardiac arrest, and in three cases cerebral edema and death. Respiratory depression recurred 13-24 hours after the ingestion in seven cases and was probably due to accumulation of difenoxine, an active metabolite of diphenoxylate. Recommended treatment is an intravenous bolus dose of naloxone, followed by a continuous intravenous infusion, prompt gastric lavage, repeated administration of activated charcoal, and close monitoring for 24 hours. 

The use of opioids in very young patients is increasing. In a review of pain management in children, various routes of administration of opioids and their associated adverse effects have been discussed (SEDA-17, 78). Attention has been drawn to the adverse effects of intravenous codeine in children and to the risk of convulsions with pethidine in neonates, because of accumulation of its metabolite norpethidine. The risk of respiratory depression with morphine was also highlighted, and morphine is recommended for use only in neonates who are being ventilated or intensively nursed. Routine use of pulse oximetry has been recommended in all children receiving opioids (SEDA-21, 86). 

The use of patient-controlled analgesia (PCA) (SEDA-15, 68) highlights the importance of adequate monitoring, in order to avoid potentially catastrophic adverse effects, such as respiratory depression. With PCA, patients generally use less morphine but still achieve the same degree of pain control (7). This supports the view that selfadministration of opioids does not put patients at risk of over-medication or drug dependence. 

Acute toxicity induced by pentazocine is primarily associated with central nervous system (CNS) effects that include dizziness, anxiety, hallucinations, mood alterations, and seizures. Respiratory depression, increased PaCOi levels, pulmonary edema, and apnea may occur. Tachycardia, increased systolic and diastolic blood pressure, pinpoint pupils, nausea, vomiting, and abdominal pain have also been reported. In a recently published case series, 40% of acute pentazocine overdose patients did not have the classic opioid toxidrome of CNS and respiratory depression with miosis. 

Maximal respiratory depression occur more rapidly with more lipid-soluble agents. After therapeutic doses, respiratory minute volume may be reduced for as long as 4-5 hours. The respiratory depression by opioids involves a reduction in the responsiveness of the brainstem respiratory centers to COj. Opioids also depress the pontine and medullary centers involved in regulating respiratory rhythmicity. 

NSAIDs are frequently used with opioids because of their lack of respiratory depression and opioid-sparing effects. However, this study demonstrates that there may be a risk of respiratory depression and other adverse effects due to persistently high levels of morphine-6-glucuronide for a number of hours after receiving an NSAID. During this time period, patients should be more closely monitored. ... 

The advantages of transdermal buprenorphine are primarily related to the convenience and improved compliance associated with a 7-day analgesic delivery system. The preparation may be particularly useful in elderly patients with moderate pain that cannot be controlled with non-opioid analgesics and others who are at risk for respiratory depression with pure mu agonists. 

Cannabinoid agonists are especially advantageous in pain management due to a relative lack of toxicity, with reported deaths from overdose rare to nonexistent. This is attributable to their low potential for respiratory depression because of the lack of CB receptors in the respiratory center of the brainstem. When used adjunctively, they are opioid-sparing and thereby reduce the risk of respiratory depression by opioids. In addition, A -THC stimulates beta endorphin production, delays development of tolerance to opioids, and limits withdrawal symptoms from opioids. 

The existence of further alternative transcripts of MOP was postulated by the observation that in knockout mice with disrupted exon 1, heroin but not morphine was still analgesically active. Based on earlier observations that the antagonist naloxazone blocked morphine-induced antinociception but not morphine-induced respiratory depression, a subdivision of the MOP in pi and p2 was proposed. However, no discrete mRNA for each of these MOP subtypes has been found. It is, however, possible that subtypes of MOPs result from heterodimerization with other opioid receptors or by interaction with other proteins. 

Fhtients receiving long-term opioid therapy rarely have problems with respiratory depression. In instances where respiratory depression occurs, administration of a narcotic antagonist (see Chap. 20) may be ordered by die primary health care provider if die respiratory rate continues to fall. 

Major gastrointestinal effects include decreased gut motility and changes in secretion of gastric and intestinal fluids. Morphine and most p receptor agonists cause pupillary constriction. Some tolerance to this effect may develop, but addicts with high opioid levels will still have miosis. Respiratory depression is the usual cause of death from opioid overdose. 

Patients who are acutely intoxicated with an opioid usually present with miosis, euphoria, slow breathing and slow heart rate, low blood pressure, and constipation. Seizures may occur with certain agents such as meperidine (Demerol ). It is critically important to monitor patients carefully to avoid cardiac/ respiratory depression and death from an excessive dose of opioids. One strategy is to reverse the intoxication by utilizing naloxone (Narcan ) 0.4 to 2 mg IV every 2 to 3 minutes up to 10 mg. Alternatively, the IM/SC route may be used if IV access is not available. Because naloxone is shorter-acting than most abused opioids, it may need to be readministered at periodic intervals otherwise the patient could lapse into cardiopulmonary arrest after a symptom-free interval of reversed... 

This class produces analgesia and has a ceiling effect on respiratory depression and lower abuse potential than morphine. However, psychotomimetic responses (e.g., hallucinations and dysphoria with pentazocine), a ceiling analgesic effect, and the propensity to initiate withdrawal in opioid-dependent patients have limited their widespread use. 

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