Sedation with opioids

Other indications. Acutely, there is sedation with anxiolysis after neurolep-tization has been started. This effect can be utilized for psychosomatic uncoupling in disorders with a prominent psychogenic component neuroleptanalgesia (p. 216) by means of the buty-rophenone droperidol in combination with an opioid tranquilization of overexcited, agitated patients treatment of delirium tremens with haloperidol as well as the control of mania (see p. 234). 

Rapid recovery and its antiemetic properties make propofol anesthesia very popular as an induction agent for outpatient anesthesia. Propofol can also be used to supplement inhalational anesthesia in longer procedures. Both continuous infusion of propofol for conscious sedation and with opioids for the maintenance of anesthesia for cardiac surgery are acceptable techniques. 

Opioids are compounds that bind one or more of the many different opioid receptors in the body. Opioids act primarily on the central nervous system. The selectivity of a given opioid for the various opioid receptors determines its characteristic activity. While many opioids are powerful analgesics, opioids often cause physical dependence and have tolerance issues. Sedation and decreased rate of breathing are also side effects associated with opioids. Despite their problems, opioids are generally the drug of choice for treating severe, acute pain. 

While NSAIDs avoid the physical dependence, sedation, and water retention problems found with opioids and glucocorticoids, NSAIDs are not without their own problems. 

The role of opioid rotation in cancer pain management has been described, highlighting the limitations of equianalgesic tablets and the need for monitoring and individualization of dose. This is particularly important when methadone is used as the opioid for conversion. The authors referred to a greater than expected potency of methadone, with excessive sedation and opioid-related adverse effects, if the switch is done on a one-to-one basis. They suggested that the calculated equianalgesic dose of methadone should be reduced by 75-90% and the dose then titrated upwards if necessary (47,48). 

BZDs OPIOIDS 1. t sedation with BZDs 2. Respiratory depressant effect of morphine is antagonized by lorazepam. 1. Additive effect both drugs are sedatives 2. Uncertain 1. Closely monitor vital signs during co-administration 2. Although this effect may be considered to be beneficial, it should be borne in mind if the combination of an opioid and BZD is used for sedation for painful procedures... 

Tetanus toxin often causes disturbances in autonomic control, resulting in sympathetic overactivity and high plasma catecholamine concentrations. The first-line treatment for autonomic dysfunction is by sedation with a benzodiazepine and opioid. Infusion of the short-acting i-blocker esmolol, or the o -adrenergic agonist clonidine, helps to control episodes of hypertension. Intravenous magnesium sulphate is also used to reduce autonomic disturbance. 

Midazolam was used in a wide range of doses (0.03-0.6 mg/kg) in 91 children undergoing diagnostic or minor operative procedures with intravenous midazolam sedation (7). Opioids were co-administered in 84% and oxygen desaturation occurred in 32%, most of whom had received high doses of opioids in addition to the midazolam. Other adverse events included airway obstruction (n = 3) and vomiting (n = 1). The presence of independent appropriate trained personnel not directly involved in performing the procedure, appropriate resuscitation... 

A strategy for controlling pain caused by malignant disease has been outlined and the classic effects that can be associated with opioid administration have been reviewed (6). These include constipation, nausea, sedation, pruritus, urinary retention, myoclonus, and respiratory depression. The latter can be life-threatening. Particular care is needed in opioid-naive individuals, those with compromised respiratory function, and elderly patients. 

Anesthetic induction with thiopental alone requires a dose of 10 to 15 mg/kg and this is not recommended. Thiopental induction typically occurs after sedation with an 012 agonist or ace-promazine with or without opioids. Guaifenesin can be used prior to thiopental at 50-100mg/kg... 

Opioid antagonists (Table 7.4), predominantly naloxone, are used clinically to reverse the effects of opiates in overdose or postoperative sedation. Naltrexone, which has oral bioavailability, is used for the treatment of narcotic addiction and alcohol dependence. As discussed below (Section 2.2.2.1), peripherally selective antagonists are being evaluated for treatment of constipation and other gastrointestinal side effects associated with opioid agonist use. 

Midazolam. Give 0.05 mg/kg (up to 0.35 mg/kg for anesthesia induction) IV over 20-30 seconds (usual adult doses vary 1 mg to maximum of 5 mg given in increments of 2.5 mg every 2 minutes lower dose in geriatric patients with maximum at 3.5 mg) or 0.07-0.1 mg/kg IM. Repeat after 10-20 minutes if needed. Continuous infusions have also been used to maintain effect with initial rates of 0.02-0.1 mg/kg/h (usual adult dose 1-7 mg/h children 1-2 mcg/kg/min) and then titrated to effect. Caution There have been several reports of respiratory arrest and hypotension after rapid intravenous injection, especially when midazolam is given in combination with opioids. Prolonged continuous infusion may lead to persistent sedation after the dmg is discontinued because midazolam accumulates in tissues. 

Metoclopramide increases the rate of absorption of oral morphine and increases its rate of onset and sedative effects. However, opioids may antagonise the effects of metoclopramide on gastric emptying. The use of droperidol with opioids can be beneficial, but an increase in sedation appears to occur. 

A single case report describes greatly increased sedation with severe CNS toxicity in a woman given pethidine after she took phe-nobarbital for two weeks. The analgesic effects of pethidine can be reduced by barbiturates. Secobarbital increases the respiratory depressant effects of morphine. Other barbiturates would also be expected to increase the CNS depressant effects of opioids. 

Increased CNS depression may occur with opioids and other CNS depressants such as hypnotics and manufacturers of several opiates specifically mention that barbiturates can potentiate sedation, respiratory depression, and hypotension. A reduction in dosage may be required. One manufacturer of methadone contraindicates the use of the injection, but not the oral solution, with other CNS depressants including barbiturates however, other manufacturers warn of the potential for increased CNS depression, but do not contraindicate barbiturates. ... 

Inereased sedative and respiratory depressant effeets are to be expeeted when benzodiazepines are used with opioids. The manufaeturers of sufentanil and alfentanil suggest that elinieally important hypotension may oeeur and this may be exaeerbated by the use of benzodiazepines it would seem prudent to be alert for this. The manufaeturers of transdermal fentanyl also warn of the possibility of respiratory depression, hypotension, profound sedation and potentially coma with concurrent CNS depressants including benzodiazepines. When such combined therapy is contemplated, the dose of one or both drugs should be significantly reduced. ... 

When used as monotherapy, IV acetaminophen does not cause excessive sedation, biliary spasm, respiratory depression, nausea, vomiting, ileus, or pruritus associated with opioids, nor the harmful cardiovascular, renal, gastrointestinal, and hematological effects associated with NSAIDs and COX-2 inhibitors. 

The Flumazenil in Intravenous Conscious Sedation with Midazolam Multicenter Study Group II. Reversal of central benzodiazepine effects by intravenous flumazenil after conscious sedation with midazolam and opioids a multicenter clinical study. Clin Ther 1992 14(6) 878-94. 

Balanced propofol sedation versus propofol monosedation for gastrointestinal endoscopy Three studies compare the efficacy and safety of procedural sedation with propofol alone or a balanced technique with propofol and/or benzodiazepine and/or opioid. Patient satisfaction was higher in the balanced propofol sedation group [82 ] but recovery time was prolonged [82, 83 ]. There was no difference in cardiorespiratory adverse events between groups [82-84 j. 

Opioid drugs are often more effective than other nonnarcotic treatments, but they are also associated with more side effects making them less suitable for many patients. Higher doses which are more effective are also associated with undesirable effects such as sedation. 

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