Respiratory depression, with

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... 

Vital Signs. Although hypertension is common and may be severe, hypotension can also occur. Tachycardia occurs in about 30 percent of cases. Severe tachypnea with respiratory rates as high as 88/min or respiratory depression with rates of 10/min or less may be seen. Respiratory arrest and cardiac arrest may occur. Hyperthermia with temperatures as high as 108.0 °F is a life-threatening event and may be associated with submassive liver necrosis (Armen et al. 1984). 

High abuse potential and risk of respiratory depression with overdose. 

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). 

Comatose, most or all reflexes absent, but without depression of respiration or of circulation Comatose, reflexes absent, respiratory depression with cyanosis or circulatory, failure and shock, or both... 

A 44-year-old white man, who had had major depression and anxiety disorder for 25 years, became drowsy after swallowing 20 tablets (10 mg) of zolpidem (44). He was not taking any other medications at the time. A few hours later he became unresponsive and comatose and developed respiratory depression with hypoxia and mild hypercapnia. He subsequently made a full recovery after appropriate medical support. 

The main life-threatening complications of heroin intoxication include acute pulmonary edema and delayed respiratory depression with coma after successful naloxone treatment. In a prospective study of the management of 160 heroin and heroin mixture intoxication cases treated in an emergency room in Switzerland between 1991 and 1992, there were no rehospitalizations after discharge... 

The main hfe-threatening complications of heroin intoxication include acute pulmonary edema and delayed respiratory depression with coma after successful naloxone treatment. In a prospective study of the management of 160 heroin and heroin mixture intoxication cases treated in an emergency room in Switzerland between 1991 and 1992, there were no rehospitahzations after discharge from the emergency room and there was only one death outside the hospital due to pulmonary edema, which occurred at between 2.25 and 8.25 hours after intoxication (36). A literature review found only two reported cases of delayed pulmonary edema, which occurred 4 and 6 hours after hospitalization. The authors recommended surveillance of a heroin user for at least 8 hours after successful opiate antagonist treatment... 

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. 

Even small doses of fentanyl can cause respiratory depression. Delayed respiratory depression can be a particular problem in the elderly, in whom the half-life is approximately three times longer than in younger patients (6). Respiratory depression has been reversed with nalbuphine doxapram could only antagonize this effect for 2-5 minutes (7). However, the need for prolonged treatment of respiratory depression with naloxone, because of pharmacokinetic variability and/or transdermal drug reservoir, has been emphasized by several authors (SEDA-16, 80) (SEDA-17, 80). 

Respiratory depression was noted in 0.24% of patients in a Chinese series of 10 978 epidural blocks (SED-12, 254) (126). Direct paralysis of respiration probably plays an important role. Respiratory depression with adverse cardiovascular effects after miscalculated dose requirements or a misplaced catheter has also been described (SEDA-22, 136). 

Konieczko KM, Jones JG, Barrowcliffe MP, Jordan C, Altman DG. Antagonism of morphine-induced respiratory depression with nalmefene. Br J Anaesth 1988 61(3) 318-23. 

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. 

In a randomized study of the respiratory effects of high concentrations of halothane and sevoflurane in 21 healthy boys undergoing inguinal or penile surgery, there was similar respiratory depression with each agent (13). Minute ventilation fell by about 50% as a result of a reduction in tidal volume, despite an increase in respiratory rate. 

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. 

Comatose, reflexes absent, respiratory depression with cyanosis or circulatory failure and shock, or both... 

The fentanyl transdermal patch releases the drug over 72 hours. The blood levels achieved will often provide analgesia for postoperative pain but at the same time will increase arterial Pco due to depression of the brain stem respiratory center. This effect has contributed to severe respiratory depression with occasional fatalities. The answer is (E). 

Cohen SE, Rolhblatt AJ, Albright GA. Early respiratory depression with epidural narcotic and intravenous droperidol. Anes esiology (1983) 59,559-60. 

Comparative studies Propofol and ketamine have been compared in procedural sedation in the Emergency Department [34. Patients were randomized to propofol 1+0.5 mg/kg every 3 minutes if needed ( =50) or the same doses of ketamine ( =47). There was a higher rate of subclinical respiratory depression with ketamine, but the number of clinical interventions in the two groups was the same. Recovery agitation was more common with the ketamine group than propofol (17% versus 4%), but procedural pain was less common (2.1% versus 6.0%). Recall and patient satisfaction were similar (13% versus 12% and 100% versus 100%). 

Respiratory effects cough suppression may suppress productive cough leading to pneumonia, dyspnea 5%, irregular breathing, and pulmonary edema. Respiratory depression with timing dependent upon route of administration (neuroaxial, epidural 5-12 hours intrathecal 4-11 hours IV, SQ 90 min IM, 30 min IV10 min). 

Butorphanol may produce respiratory depression, with other medications with significant CNS action and in patients with CNS or respiratory diseases. 

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. 

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. 

Stamer UM, Stuber F, Muders T, Musshoff F. Respiratory depression with tramadol in a patient with renal impairment and CYP2D6 gene duplication. Anesth Analg 2008 107(3) 926-9. 

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