Propofol administration

Propofol infusion syndrome can present with one component only, such as lactic acidosis (954) or rhabdomyolysis (955) (see below). It has been suggested that patients who are susceptible to metabolic acidosis or rhabdomyolysis after propofol administration may have subclinical forms of mitochondrial diseases that affect either the respiratory chain complex or fatty acid oxidation (956). In order to minimize the development of propofol infusion syndrome as a potentially lethal complication, a maximum dose of 3 mg/kg/hour has been recommended for sedation in intensive care patients. 

Asirvatham SJ, Johnson TW, Oberoi MP, Jackman WM. Prolonged loss of consciousness and elevated porphyrins following propofol administrations. Anesthesiology 1998 89(4) 1029-31. 

Wingfield TW. Pancreatitis after propofol administration is there a relationship Anesthesiology 1996 84(1) 236. 

Betrosian AP, Balia M, Papanikolaou M, Kofinas G, Georgiadis G. Post-operative pancreatitis after propofol administration. Acta Anaesthesiol Scand 2001 45(8) 1052. 

Manataki AD, Arnaoutoglou HM, Tefa LK, Glatzounis GK, Papadopoulos GS. Continuous propofol administration for suxamethonium-induced postoperative myalgia. Anaesthesia 1999 54(5) 419-22. 

The manufacturer notes that the required induction dose of propofol may be reduced in patients who have received opioids, and that these drugs may increase the anaesthetic and sedative effects of propofol, and also cause greater reductions in blood pressure and cardiac output. They also state that the rate of propofol administration for maintenance of anaesthesia may be reduced in the presence of supplemental analgesics such as opioids. ... 

Mice lacking the 8 subunit, which is mainly expressed in cerebellum and thalamus, display an attenuation of ssatrighting reflex time following the administration of the neurosteroids, alphaxalone and pregnanolone, while the responses to propofol, etomindate, ketamine and the benzodiazepine midazolam were unaffected. This demonstrates the role of GABAa receptors containing the 8 subunit for neurosteroid action. 

Propofol can be used for induction as well as maintenance of anesthesia. It is very lipophilic and induction of anesthesia takes place within 30 seconds. After a single dose the patient awakes in approximately 5 minutes and after anesthesia by continuous intravenous administration of longer duration recovery may take 10-15 minutes. It can be used in combination with the usual range of premedications, analgesics, muscle relaxants and inhalation anesthetic agents. 

Unconsciousness is usually achieved 20-40 seconds after an induction dose. Transfer to the CNS is slower than with thiopentone and there is a delay in disappearance of the eyelid reflex, normally used as a sign of unconsciousness after administration of other intravenous anaesthetics. Overdosing of propofol may occur if this sign is used loss of verbal contact is a more reliable end-point. 

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. 

Ketamine has been traditionally contraindicated in patients with increased ICP or reduced cerebral compliance because it increases CMR02, CBF and ICP. These deleterious effects can be antagonised by the concomitant administration of propofol, or thiopentone, and benzodiazepines. Furthermore, ketamine is an antagonist at the NMDA receptor. Nevertheless, ketamine can adversely affect neurological outcome in the presence of brain ischaemia. 

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. 

Effects on respiration are similar to those of thiopental at usual anesthetic doses. However, propofol causes a marked decrease in systemic blood pressure during induction of anesthesia, primarily through decreased peripheral resistance. In addition, propofol has greater negative inotropic effects on the heart than etomidate and thiopental. Apnea and pain at the site of injection are common adverse effects of bolus administration. Muscle movements, hypotonus, and (rarely) tremors have also been reported following its use. Clinical infections due to bacterial contamination of the propofol emulsion have led to the addition of antimicrobial adjuvants (eg, ethylenediaminetetraacetic acid and metabisulfite). 

Propofol [pro POF ol] is an IV sedative/hypnotic used in the induction or maintenance of anesthesia. Onset is smooth and occurs within about 40 seconds of administration. Supplemenation with narcotics for analgesia is required. While propofol facilitates depression in the CNS, high plasma levels can cause excitation. Propofol decreases blood pressure without depressing the myocardium. It also reduces intracranial pressure. 

Propofol has a remarkably simple structure resembling that of phenol disinfectants. Because the substance is water-insoluble, an injectable emulsion is prepared by means of soy oil, phosphatide, and glycerol. The effect has a rapid onset and decays quickly, being experienced by the patient as fairly pleasant. The intensity of the effect can be well controlled during prolonged administration. Possible adverse reactions include hypotension and respiratory depression, and a potentially fatal syndrome of bronchospasm, hypotension, and erythema. 

Burns R, McCrae AF, Tiplady B. A comparison of target-controlled with patient-controlled administration of propofol combined with midazolam for sedation during dental surgery. Anaesthesia 2003 58 170-6. 

---