Propofol Opioids

Lichtenbelt B-J, Mertens M, Vuyk J. Strategies to optimise propofol-opioid anaesthesia. Chn Pharmacokinet (2004) 43, 577-93. 

Vuyk J. Clinical interpretation of pharmacokinetic and pharmacod3mamic propofol-opioid interactions. Acta Anaesthesiol Belg (2001) 52, 445-51. 

Opioids play an important role in anesthetic practice. Opioid analgesics potentiate the efficacy of anesthetics. They can be given as part of the premedication as well as during the operation. Examples of short acting agents with high potency are fentanyl, sufentanyl, alfentanil and remifentanil. Because of their hemodynamic stability these agents can be used for patients with compromised myocardial function. Respiration must be maintained artificially and may be depressed into the postoperative period. They are usually supplemented with inhalation anesthetic, benzodiazepines or propofol. 

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. 

Propofol is primarily a hypnotic drug with substantial cardiorespiratory depressant actions and with no ability to produce neuromuscular blockade. While propofol lacks analgesic properties, its use permits lower doses of opioids. Likewise, less propofol is required for adequate hypnosis when it is administered with opioids. Thus, it is said that propofol and opioids interact synergistically. 

Answer This feature of bradycardia is typical of patients who take (3-blockers, which should be continued so they result ultimately in better anesthetic management. The drugs given could have been modified (i.e., etomidate instead of propofol, which does not raise or may cause a slower heart rate). The potent opioids in the fentanyl family all cause vagal transmitted bradycardia. The muscle relaxant vecuronium (norcuron) has no effect on heart rate and could have been replaced by pancuronium, which has a vagolytic effect and will counter bradycardia in the usual induction bolus doses. 

Emergence delirium with restlessness, disorientation and unpleasant dreams or hallucinations may occur for up 24 hours following ketamine administration. Their incidence is reduced by psychological preparation of the patient, avoidance of verbal and tactile stimulation during the recovery period, or by concomitant administration of opioids, benzodiazepines, propofol or physostigmine. However, unpleasant dreams may persist. 

Many of the drugs used in modern anaesthetic practice have an effect on the CT7 and vomiting centre either directly or indirectly, e.g. stimulation of the vestibular apparatus, stimulation of the CTZ by opioid agonist drugs, and an anti-emetic effect of propofol or emetogenic effect of nitrous oxide. Propofol... 

Recovery is sufficiently rapid with most intravenous drugs to permit their use for short ambulatory (outpatient) surgical procedures. In the case of propofol, recovery times are similar to those seen with sevoflurane and desflurane. Although most intravenous anesthetics lack antinociceptive (analgesic) properties, their potency is adequate for short superficial surgical procedures when combined with nitrous oxide or local anesthetics, or both. Adjunctive use of potent opioids (eg, fentanyl, sufentanil or remifentanil see Chapter 31) contributes to improved cardiovascular stability, enhanced sedation, and perioperative analgesia. However, opioid compounds also enhance the ventilatory depressant effects of the intravenous agents and increase postoperative emesis. Benzodiazepines (eg, midazolam, diazepam) have a slower onset and slower recovery than the barbiturates or propofol and are rarely used for induction of anesthesia. However, preanesthetic administration of benzodiazepines (eg, midazolam) can be used to provide anxiolysis, sedation, and amnesia when used as part of an inhalational, intravenous, or balanced anesthetic technique. 

The technique typically involves the use of intravenous midazolam for premedication (to provide anxiolysis, amnesia, and mild sedation) followed by a titrated, variable-rate propofol infusion (to provide moderate to deep levels of sedation), and a potent opioid analgesic or ketamine (to minimize the discomfort associated with the injection of local anesthesia and the surgical manipulations). 

Deep sedation is similar to a light state of general (intravenous) anesthesia involving decreased consciousness from which the patient is not easily aroused. Because deep sedation is often accompanied by a loss of protective reflexes, an inability to maintain a patent airway, and lack of verbal responsiveness to surgical stimuli, this state may be indistinguishable from intravenous anesthesia. Intravenous agents used in deep sedation protocols include the sedative-hypnotics thiopental, methohexital, midazolam, or propofol, the potent opioid analgesics, and ketamine. 

Etomidate is a carboxylated imidazole that can be used for induction of anesthesia in patients with limited cardiovascular reserve. Its major advantage over other intravenous anesthetics is that it causes minimal cardiovascular and respiratory depression. Etomidate produces a rapid loss of consciousness, with minimal hypotension even in elderly patients with poor cardiovascular reserve. The heart rate is usually unchanged, and the incidence of apnea is low. The drug has no analgesic effects, and coadministration of opioid analgesics is required to decrease cardiac responses during tracheal intubation and to lessen spontaneous muscle movements. Following an induction dose, initial recovery from etomidate is less rapid (< 10 minutes) compared with recovery from propofol. 

A relatively large number of studies have investigated the effects of opioids on tests requiring focused attention. Morphine (2.5 to 10 mg, IV)185 and propofol (70 mg, IV)193 impaired an auditory simple reaction time test, and fentanyl (1 to 2.5 ng/ml, IV)182 impaired a visual choice reaction time test. Jenkins et al.197 reported that IV (3 to 20 mg) and smoked (2.6 to 10.5 mg) heroin impaired performance on a simple visual reaction time task. However, other studies reported no effect of butorphanol (0.5 to 2.0 mg, IV),186 fentanyl (25 to 100 pg, IV),191 meperidine (0.25 to 1.0 mg, IV),192 and nalbuphine (2.5 to 10 mg, IV)189 on an auditory simple reaction time test. It may be... 

Numerous studies have reported that performance on the DSST was impaired by various opioids, including morphine (2.5 to 10 mg),185,198 fentanyl (1 to 2.5 ng/ml),182 pentazocine (30 mg),184 butorphanol (0.5 to 2 mg),186 dezocine (2.5 to 10 mg),187 propofol (22 to 70 mg),193,199 nalbuphine (2.5 to 10 mg, IV),189 and the combination of fentanyl (50 pg) plus propofol (35 mg).194 In contrast, meperidine was found to have no effect on the DSST.192 Because the DSST is a timed test, it would appear that opioids slow speeded responses in a fairly consistent manner in opioid-naive subjects. However, in opioid abusers or opioid-dependent persons, Preston and colleagues have reported no effect on DSST performance of several opioids, including morphine (7.5 to 30 mg, IM),200 hydro-morphone (0.125 to 3 mg, IM),201 buprenorphine (0.5 to 8 mg, IM),202 pentazocine (7.5 to 120 mg, IM),203 butorphanol (0.375 to 1.5 mg, IV),204 and nalbuphine (3 to 24 mg, IM).205... 

Several drugs are used intravenously, alone or in combination with other drugs, to achieve an anesthetic state (as components of balanced anesthesia) or to sedate patients in intensive care units who must be mechanically ventilated. These drugs include the following (1) barbiturates (thiopental, methohexital) (2) benzodiazepines (midazolam, diazepam) (3) opioid analgesics (morphine, fentanyl, sufentanil, alfentanil, remifentanil) (4) propofol (5) ketamine and (6) miscellaneous drugs (droperidol, etomidate, dexmedetomidine). Figure 25-2 shows the structures of... 

Recovery is sufficiently rapid with many intravenous drugs to permit their extensive use for short ambulatory (outpatient) surgical procedures. In the case of propofol, recovery times are similar to those seen with the shortest-acting inhaled anesthetics. The anesthetic potency of intravenous anesthetics, including thiopental, ketamine, and propofol, is adequate to permit their use as the sole anesthetic in short surgical procedures when combined with nitrous oxide and opioid analgesics. 

Many diagnostic, therapeutic, and minor surgical procedures require neither general anesthesia nor the availability of specialized equipment and facilities necessary for inhaled anesthesia. In this setting, regional or local anesthesia supplemented with midazolam or propofol and opioid analgesics may be a more appropriate and safer approach than general anesthesia. 

Usually intravenous pre-oxygenation followed by a small dose of an opioid, e.g., fentanyl or alfentanil to provide analgesia and sedation, followed by propofol or, less commonly, thiopental or etomidate to induce anaesthesia. Airway patency is maintained with an oral airway and face-mask, a laryngeal mask airway (LMA), or a tracheal tube. Insertion of a tracheal tube usually requires paralysis with a neuromuscular blocker and is undertaken if there is a risk of pulmonary aspiration from regurgitated gastric contents or from blood. 

Anaesthesia in MH-susceptible patients is achieved safely with total intravenous anaesthesia using propofol and opioids. Dantrolene for intravenous use must be available in every surgical theatre. The relation of malignant hyperthermia syndrome with neuroleptic malignant syndrome (for which dantrolene may be used as adjunctive treatment, see p. 388) is uncertain. 

Sedation in critical care units is used to reduce patient anxiety and improve tolerance to tracheal tubes and mechanical ventilation. Whenever possible, patients are sedated only to a level that allows them to open their eyes to verbal command oversedation is harmful. Commonly used drugs include propofol and midazolam, and opioids such as fentanyl, alfentanil, or morphine. 

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