Awake intubation increases intracranial pressure without affecting cerebral blood flow velocity in infants

Tracheal intubation is frequently required in neonatal anaesthetic practice. Awake intubation is one method of securing the airway and in certain circumstances, for many anaesthetists, can be preferable to intubation following induction of anaesthesia. Previous studies have inferred that the elevation in anterior fontanelle pressure observed during tracheal intubation in neonates was caused by an increase in cerebral blood flow although it was never measured. In this study, direct methods were used to observe changes in the cerebral circulation. Thirteen neonates, ASA I to III (E), aged from 1 to 34 days of age were studied. Patients were randomized to receive either tracheal intubation awake or following induction of anaesthesia with thiopentone 5 mg · kg^{? 1} and succinylcholine 2 mg · kg^?1. Heart rate, systolic arterial blood pressure, anterior fontanelle pressure, cerebral blood flow velocity (using transcranial Doppler sonography) and oxygen saturation were recorded at the following intervals: baseline (not crying), after intravenous atropine 0.02 mg · kg^{? 1}, during laryngoscopy, immediately after insertion of the endotracheal tube, one and five minutes later. The use of atropine masked the cardiovascular responses to intubation. Whereas the change in anterior fontanelle pressure from baseline was different between the groups (P < 0.05), the cerebral blood flow velocity variables were not. The rise in anterior fontanelle pressure seen in the awake group may be attributed to a reduction of the venous outflow from the cranium thereby increasing cerebral blood volume and sub-sequently the intracranial pressure.     

The incidence of masseter muscle rigidity after succinylcholine in infants and children

To determine whether the incidence of masseter muscle rigidity is affected by the anaesthetic induction sequence, we prospectively studied for ten months the anaesthetic course in 5,641 infants and children who received muscle relaxation to facilitate tracheal intubation. The anaesthetic induction sequence consisted of intravenous sodium thiopentone (STP) 5 mg · kg^?1 alone, halothane induction alone 1–4%, or halothane followed by STP. Inhalational inductions with halothane included nitrous oxide and oxygen. Tracheal intubation was facilitated by either intravenous succinylcholine (Sch) at least 1.5 mg · kg^?1 or by a non-depolarizing muscle relaxant. The induction sequence and all episodes of MMR were recorded. Ninety percent of the patients received Sch and 10% received a non-depolarising agent. Of those who received Sch, 88% (5,064 patients) were anaesthetised with STP and 12% (607 patients) were anaesthetised with halothane alone or halothane followed by STP Masseter muscle rigidity was defined clinically by the transient inability to distract the mandible from the maxilla such that the mouth could not be opened or could only be opened with force. No children anaesthetised with STP followed by Sch developed MMR. One child (0.9%) developed MMR after halothane and Sch and two developed MMR after halothane, STP and Sch (0.4%). The incidence of MMR after Sch was less with STP than with halothane alone or with halothane and STP (P < 0.025). The peak CPK values in the three children who developed MMR were 17,580 IU · L^?1 after halothane and Sch, and 7,280 IU·^?1 and 3,273 IU ·^?1 after halothane, STP and Sch. There was no evidence of MH reactions in these patients. No child developed malignant ventricular arrhythmias or cardiac arrest after Sch or a non-depolarising neuromuscular relaxant. There were no episodes of succinylcholine apnoea. We conclude that MMR is less likely to occur following STP and Sch than after halothane and Sch.     

Epidural opioid analgesia after Caesarean section: a comparison of patient-controlled analgesia with meperidine and single bolus injection of morphine

The quality of analgesia, patient satisfaction and incidence of side effects following a single bolus of epidural morphine were compared with patient-controlled epidural analgesia (PCEA) with meperidine during the first 24 hr after elective Caesarean section. Seventy-five women were randomly assigned to three equal groups. Group 1 received 30 mg epidural meperidine after delivery and PCEA with meperidine; Group 2 received 3 mg epidural morphine after delivery and PCEA with saline in a double-blind fashion. Group 3 received 3 mg epidural morphine after delivery without saline PCEA. Visual analogue pain scores (VAS) were higher with PCEA meperidine from 8–16 hr postoperatively (P < 0.05) than in both epidural morphine groups. Two patients in Group 1 and one in Group 3 required supplemental parenteral analgesia. The incidence of nausea was 16% in Group 1, compared with 52% in Group 2 and 56% in Group 3 (P < 0.01). Pruritus occurred in 24% of Group 1 patients, 84% of patients in Group 2 and 68% of patients in Group 3 (P< 0.001). Forty-six percent of patients in Group 1 were very satisfied with pain management, compared with 77% in Group 2 and 79% in Group 3. Nurse workload was higher in the PCEA study groups than in Group 3 (P< 0.05). A single bolus of epidural morphine provides superior analgesia and satisfaction at low cost, but with a higher incidence of nausea and pruritus than PCEA with meperidine.     

Changing Mallampati score during labour

We present the case of a changing Mallampati score during the course of labour in a healthy primigravida. On admission to hospital, the airway was assessed as Mallampati class I–II. At 5 cm cervical dilation, the woman began to bear down strenuously and continued this despite being advised of the inherent hazard. At 8 cm dilation, Caesarean delivery was contemplated because of fetal heart rate decelerations. Repeat airway evaluation revealed marked oedema of the lower pharynx giving rise to a Mallampati score of III–IV. Improvement of the fetal heart rate tracing permitted vaginal delivery under local infiltration. Postpartum, the Mallampati score was still III–IV However, 12 hr later it had returned to the admission classification of I–II. We recommend that, in addition to the usual airway evaluation on admission, the assessment be repeated in the obstetric patient before induction of general anaesthesia.     

Exacerbation of postdural puncture headache after epidural blood patch

The purpose of this report is to describe a new complication of epidural blood patch for inadvertent dural puncture. A dural tap in an obstetric patient was managed initially with a prophylactic blood patch via the epidural catheter. Despite this, 48 hr later, she developed post-dural puncture headache, neck, and shoulder pain, and was given a second epidural blood patch. This was followed by an immediate and severe exacerbation of her symptoms, which later resolved after the administration of diclofenac. There were no further sequelae. Although severe complications of epidural blood patch are rare, they are alarming. Exacerbation of the original symptoms of post-dural puncture headache caused by, or following, epidural blood patching has not previously been reported.     

Absence of antitrifluoroacetate antibody after halothane anaesthesia in patients exhibiting no or mild liver damage

It has been shown that the circulating antibodies, which bind to rat hepatic microsomal proteins obtained after in vivo exposure to halothane, are detectable by immunoblotting in patients with “halothane hepatitis (HH),” and that rabbit immunized anti-sera against trifluoroacetylated rabbit serum albumin (TFA-RSA) recognizes rat microsomal distorted polypeptides in almost the same way as do sera from patients with HH. In this paper, we report first the development of a novel method of synthesizing TFA-RSA using p-nitrophenyl TFA, and second the results of tests for circulating anti-TFA antibodies in the serum of 86 patients who had received halothane anaesthesia and developed no (67 patients) or mild (19 patients, the maximum activity of serum alanine aminotransaminase 519 IU · L^?1) liver damage. Serum was selected from stored sera of post-transfusion patients. The new method of synthesizing TFA-RSA was convenient and was able to be done at neutral pH. Rabbit sera obtained after immunization with the newly synthesized TFA-RSA recognized the same polypeptides (109 kDa, 92 kDa, 80 kDa, 76 kDa, 64 kDa and 59 kDa) as the established anti-sera against TFA-RSA, and these reactions were inhibited in the presence of TFA-lysine. Circulating antibodies were not detected in our patients who had developed no or mild liver damage. The present finding supports the hypothesis that the appearance of circulating antibodies against microsomal distorted proteins are specific to patients with HH. Furthermore, we have shown here that the halothane-induced mild increase in ALT activity is not associated with the appearance of those circulating antibodies, supporting the pathophysiological difference between HH and halothane-induced mild hepatic damage.     

Adjuvant propofol enables better control of nausea and emesis secondary to chemotherapy for breast cancer

We investigated the prophylactic antiemetic effect of added lowdose infusion of propofol in patients exhibiting nausea and vomiting refractory to dexamethasone and serotonin antagonist during non-cisplatin chemotherapy for breast cancer. In a prospective open longitudinal study, 117 patients who had more than five episodes of nausea and vomiting in their first chemotherapy cycle during the first 24 hr completed the study. They received in addition to the usual prophylactic antiemetic regimen a continuous intravenous infusion of 1 mg · kg^?1 · hr^?1 propofol started four hours before chemotherapy and continued up to 24 hr for the two subsequent cycles. The number of vomiting / nausea episodes, level of sedation, patient activity, appetite and preference for future chemotherapy cycles were assessed. In the propofol supplemented cycles 90 and 80% of patients, during the 1st and 2nd propofol-assisted cycle respectively, were free of nausea and vomiting during the first 24 hr after chemotherapy. Patients were more frequently active and had more appetite during the propofol-assisted cycles. No propofol-associated side effects were observed. We conclude that the addition of a subhypnotic infusion of propofol enables better control of nausea and vomiting caused by non-cisplatin chemotherapy in the first 24 hr post-treatment.     

Hydromorphone patient-controlled analgesia (PCA) after coronary artery bypass surgery

We conducted a study to compare the effectiveness of patientcontrolled analgesia (PCA) technique to conventional analgesic therapy (CAT) after coronary artery bypass graft (CABG). The PCA group received hydromorphone 0.1 mg · hr^?1 basal infusion and bolus doses of 0.2 mg Q 5 min (maximum 1.2 mg · hr^?1) while the CAT group received morphine 2.5 mg iv Q 30 min prn until extubation followed by prn meperidine 1 mg · kg^?1 im Q4 hr or acetaminophen 325 mg with codeine 30 mg po (1 or 2 tablets) when oral intake was possible. The degree of pain was assessed using a Visual Analogue Scale (VAS) starting after extubation and every 6–8 hr for the next 60 hr. Holter monitoring was initiated one hour after patient arrival in the Intensive Care Unit (ICU) and continued for 72 hr. Other measured variables were pulmonary function, sedation, side effects and total opioid requirements. Results show that the day-to-day VAS pain score decreased in the PCA group (P < 0.001) while it remained unchanged in CAT patients. The PCA patients had lower VAS pain scores at extubation (P < 0.05). During the third postoperative day, the PCA group had a lower VAS pain score, a lower incidence of severe pain defined as a score > 5 on the VAS scale, and a reduced incidence of myocardial ischaemia (P < 0.01). However, there was no difference in the duration, severity, area under the curve (AUC), or heart rate during ischaemic events. Postoperative pulmonary function was abnormal in both groups (NS) with minimal recovery by the fourth day. Opioid requirements, incidence of side effects and the degree of sedation were similar. We conclude that the PCA technique for analgesia provided slightly better results. The finding of a reduced incidence of myocardial ischaemia in the PCA group warrants further clinical investigation.     

Neuroleptic malignant syndrome and mivacurium: a safe alternative to succinylcholine?

Neuroleptic malignant syndrome (NMS) and malignant hyperthermia (MH) may have a common pathogenic mechanism; therefore, it has been suggested that known triggering agents for MH (such as succinylcholine) should be avoided in patients with NMS. Electroconvulsive therapy (ECT) continues to play a major therapeutic role in contemporary psychiatry, and succinylcholine has been the muscle relaxant of choice in attenuating violent muscle contractions induced by ECT. Mivacurium is a nondepolarizing muscle relaxant with a relatively rapid onset and a short duration of action, and to date it has been proved safe in MH- susceptible patients. In this case report, following succinylcholine use during ECT, a patient with NMS developed an increase in temperature and serum creatine kinase (CK) level, possibly due to an MH reaction. Since the patient’s mental status necessitated further ECT, mivacurium was administered during subsequent treatments and resulted in effective attenuation of muscle contractions without elevation of patient temperature or CK levels. In addition, there was no marked prolongation of the anaesthetic. Mivacurium is a suitable agent for patients with NMS undergoing ECT, as it has not been associated with precipitation of an MH response.     

Opisthotonos following propofol: A nonepileptic perspective and treatment strategy

In this report of opisthotonos during recovery from propofol anaesthesia, we relate clinical observations with scientific considerations, and propose a strategy for treatment of this rare side effect. Following a brief operative procedure, a healthy 29-yr-old woman developed recurrent opisthotonos while recovering from anaesthesia with alfentanil, propofol, and nitrous oxide. In contrast to accumulating reports, the patient remained conscious during each episode of back extension and retrocollis. The preservation of consciousness and similarities to strychnine-induced opisthotonos suggest to us that the mechanism may have a brainstem and spinal origin. Recent investigations show that propofol potentiates the inhibitory transmitters glycine and γ-aminobutyric acid (GABA) which would enhance spinal inhibition during anaesthesia. Postanaesthetic opisthotonos, however, may be due to a propofol-induced tolerance to inhibitory transmitters. This rebound phenomenon would lead to an acute, enduring refractoriness in inhibitory pathways of the brainstem and spinal cord, resulting in increased activity of extensor motoneurons. We recommend a therapeutic strategy that restores inhibition by glycine and GABA at multiple sites; the preferred therapeutic agents would be diazepam and physostigmine. The episodes are usually short-lived, but two of the reviewed 17 patients developed recurrent retrocollis for four and 23 days following antiepileptic drug therapy. Since high doses of phenytoin and carbamazepine can result in opisthotonos, we recommend that anticonvulsants be reserved for post-anaesthetic patients with electroencephalographic evidence of seizure activity.     

Cytomegalovirus prostatitis

We report the case of a patient undergoing chemotherapy for multiple myeloma discovered to have cytomegalovirus prostatitis. The findings of a hypoechoic prostatic lesion on ultrasound and a slightly elevated prostatic specific antigen of 4.6 ng/ml prompted a prostate biopsy. Cytopathologic examination and immunohistochemical staining demonstrated cytomegalovirus within the prostate. This virus is a common pathogen in the immunosuppressed patient, but its presence in the male genital tract is relatively rare. No previous reports of biopsy-proven cytomegalovirus prostatitis appear in the literature. The relationship of cytomegalovirus to the prostate is discussed in detail.     

Drug allergies in the surgical population

Many patients claim to have drug allergies. However, the signs and symptoms of “allergic reactions” are seldom documented and the drug allergies are rarely properly assessed. The goal of this study was to determine the incidence of claimed “drug allergies” in a surgical population. After obtaining institutional approval, the study was carried out at five hospitals affiliated with Dalhousie University. Patients were interviewed by the investigators during the preoperative anaesthetic evaluation over six months and all signs and symptoms of drug reactions were recorded. The validity of the claimed allergy was based on the history. The allergies were assigned to one of three groups: (1) High probability of an allergic reaction: one or more of the signs and symptoms typical of an immunological reaction, with or without a family history, or a history of atopy: (ii) Low probability of an allergic reaction: signs and symptoms of the reaction were predictable reactions or side effects of the drug, without the occurrence of reactions mentioned above; or (iii) Unknown status. no information concerning the reaction of history was available. Of 1818 adult and paediatric patients (914 female/904 male) interviewed, 511 (28.1%) claimed to have one or more drug allergies (a total of 671 allergies). More women than men claimed to have drug allergies (60.3% vs 39.7%) and there was a positive correlation between age, number of medications and reported drug allergies. Antibiotics (50%), opioids (27%), nonsteroidal antiinflammatory agents (10%), and sedatives (5%) accounted for 92% of all claimed drug allergies. Overall, 50% of claimed allergies had a high probability of true allergic reactions. The majority of antibiotics (75%) were associated with a high probability for true allergic reactions, but most of the other drug classes, such as opioids (83%), NSAIDs (64%) and sedatives (67%), were associated with a low probability for true allergic reactions. Our findings suggest a serious problem in the “labelling” of our patients as having drug allergies. Patients and health care personnel should be educated in the differentiation between predictable adverse drug reactions and true allergic drug reactions.     

Anaesthesia for the patient with neonatal adrenoleukodystrophy

The authors present and discuss the care of a nine-month-old with neonatal adrenoleukodystrophy who required general anaesthesia for gastrointestinal endoscopy. Neonatal adrenoleukodystrophy is an inherited disorder of peroxisomal enzymes. Anaesthetic care may be affected by the presence of hypotonia, liver function abnormalities, gastroesophageal reflux, and impaired adrenocortical function. Preoperative sedation is contraindicated because of the risk of precipitating airway obstruction due to preexisting hypotonia. Anaesthetic induction and tracheal intubation should be performed to minimize the risk for aspiration of gastric contents. The choice of muscle relaxant should take into account the preexisting hypotonia as well as the possibility of hyperkalaemia in response to succinylcholine. Anaesthetic agents known to decrease the seizure threshold should be avoided in patients with a seizure disorder. In addition, anaesthetic agents that rely on the liver for metabolism should be used with caution in patients with cirrhosis. When time permits, these patients should be screened for adrenocortical insufficiency before surgery, and perioperative steroid coverage is advisable when preoperative testing of adrenocortical function is not feasible. While these patients eventually die after progressive deterioration, full recovery from the effects of anaesthesia and surgery can be achieved with attention to neurological, metabolic, and physical problems.     

Mechanisms of inhibition of endothelium-dependent relaxation by halothane,isoflurane, and sevoflurane

Volatile anaesthetics inhibit endothelium-dependent relaxation, but the underlying mechanism(s) have not been clarified. In an attempt to elucidate the mechanism(s), we determined the effects of halothane, isoflurane and sevoflurane on relaxation induced by acetylcholine and sodium nitro-prusside (SNP) and the cGMP formation elicited by exogenous nitric oxide (NO) and SNP in rat aortas. Acetylcholine (10^?7?10^?5M) - induced relaxation was attenuated by halothane (2%), isoflurane (2%) and sevoflurane (4%). SNP (10^?8 M) - induced relaxation was reduced by halothane (2%), but not by isoflurane (2%) or sevoflurane (4%). The cGMP level of NO-stimulated aorta was reduced by halothane (2%) and sevoflurane (4%), but not by isoflurane (2%). The cGMP level of SNP (10^?7 M) - stimulated aorta was reduced by halothane (2%), but not by isoflurane (2%) and sevoflurane (4%). We conclude that the mechanisms responsible for the inhibition of endothelium-dependent relaxation differ among anaesthetics. Isoflurane inhibits the relaxation mainly by inhibiting the formation of NO in the endothelium. In contrast, the effect of halothane on endotheliumdependent relaxation may be largely due to the inhibition of action of NO in the vascular smooth muscle and the effect of sevoflurane may be to inactivate NO or to inhibit the action of NO.     

Duration of decubitus position after epidural blood patch

Thirty patients presenting with post-dural puncture headache (PDPH) were prospectively studied to determine the influence of the duration of the decubitus position after epidural blood patch on the efficacy of treatment. All patients received 12 ml of autologous blood. They were randomly distributed into three groups of ten patients. Patients in Group 1 were maintained in a decubitus position for 30 min after the epidural injection of autologous blood in the epidural space. Patients in Group 2 were maintained for 60 min in decubitus and patients in Group 3 for 120 min. Post-dural puncture headache was evaluated using a visual analogue scale before the epidural blood patch, at the time of initially adopting a standing position after the blood patch, and 24 hr later. The severity of PDPH in the three groups was reduced at the time of initially adopting a standing position and after 24 hr, in comparison with pre-blood patch VAS (P < 0.001). Patients in Group 3 presented less severe PDPH than patients in Group 1 at the time of initially standing up and 24 hr later (P < 0.05). We conclude that epidural blood patch was effective in treating PDPH but that the maintenance of a decubitus position for at least one hour and preferably for two hours after the blood patch was more effective than maintenance for 30 min.     

Succinylcholine-induced cardiac arrest in children with undiagnosed myopathy

Two paediatric cases are reported in which unexpected, life-threatening arrhythmias occurred. Routine induction of general anaesthesia with thiopentone, 5 mg · kg^?1, in one and with halothane in the other, and succinylcholine 1.25 – ?1.5 mg · kg^?1 iv was followed by the development of wide complex tachyarrhythmia with hypotension in the first case and asystole in the second case despite pre-treatment with atropine in both cases. The first patient was resuscitated with tracheal intubation, 100% oxygen, manual ventilation and intravenous lidocaine and bicarbonate. The second patient required intubation, manual ventilation, 12 min of CPR and iv calcium, epinephrine and bicarbonate, as well as DC counter shock. Neither patient received dantrolene. Early recovery in both patients was uneventful with no neurological sequelae. Subsequent investigations revealed the presence of a dystrophin-deficient muscular dystrophy, Duchenne muscular dystrophy and Becker muscular dystrophy respectively, previously unsuspected, in both patients. The aetiology of the observed arrhythmias was presumably hyperkalaemia, secondary to succinylcholine-induced rhabdo-myolysis. It is suggested that when faced with sudden, life-threatening arrhythmias following succinylcholine at induction of anaesthesia for paediatric patients, clinicians should include occult myopathy in the differential diagnosis, and thus consider the aggressive management of hyperkalaemia in addition to basic resuscitative efforts.     

Phaeochromocytoma presenting as acute hyperamylasaemia and multiple organ failure

Phaeochromocytoma may present in many different ways. We report an unusual presentation of phaeochromocytoma in a man with hyperamylasaemia and multiple organ failure thought to be due to acute relapsing pancreatitis. Abdominal ultrasound and computerised tomography (CT) examinations revealed a mass at the tail of the pancreas. Fine needle biopsy of the mass precipitated headache, intense vasoconstriction and labile blood pressure. He proceeded to laparotomy, at which an 8 × 9 cm mass was found to be replacing the left adrenal gland. Histological examination revealed a phaeochromocytoma. This case illustrates that hyperamylasaemia and multiple organ failure may be unusual presentations of phaeochromocytoma and phaeochromocytoma should be considered in the differential diagnosis of a peripancreatic mass found by ultrasound or CT.     

Transcranial doppler sonography during isoflurane/N2O anaesthesia and surgery: flow velocity, “vessel area” and “volume flow”

Transcranial Doppler sonography (TCD) constitutes an advance in noninvasive monitoring of the cerebral circulation. However, as long as the diameter and cross-sectional area of the insonated middle cerebral artery (MCA) remain unknown, the derived flow velocities (v) are not informative. It is not known how the human MCA is influenced by anaesthetic agents. However, a TCD-modification allows noninvasive determination of “vessel area” (VA) and “volume flow” (VF) in MCA by analysing the backscattered Doppler power. This investigation evaluates the effects of isoflurane (in combination with N₂O and surgery) on v, VA and VF. In 14 patients (ASA I) scheduled for minor surgical or gynaecological operations, anaesthesia was induced with droperidol, alfentanil, thiopentone and vecuronium. After intubation ventilation with N₂O:O₂ = 3:2 was adjusted, to maintain endexpiratory carbon dioxide (FECO₂) constant between 4 and 5%. Baseline values of heart rate (HR), oscillometric mean arterial pressure (MAP), and TCD variables (v, VA VF) were measured before adding 2.4% isoflurane to the inspiratory mixture. Further measurementswere made 3, 6,10, and 20 min after starting isoflurane. Surgery commenced between the sixth and tenth minute after isoflurane application. The MAP,FeCO₂, and v showed only minor alterations; HR increased after 6, 10 and 20 min. Transcranial “vessel area” and “volume flow” showed increases after isoflurane inhalation. The increase of “vessel area” supports the assumption that isoflurane greater than 1 MAC dilates large human cerebral arteries, so that if flow velocities are considered alone, alterations of cerebral blood flow may easily be underestimated.     

Anaesthetic management of an asthmatic child for appendicectomy

A 13-yr-old boy was scheduled for emergency appendicectomy because of abdominal pain. His preoperative medical history was complicated by a recent hospital admission for management of asthma. He had presented to hospital seven days earlier because of dyspnoea, tachypnoea and oxygen desaturation to 77% on room air. Following admission, he required intensive non-ventilatory management of his asthma, including intravenous salbutamol, methylprednisolone, and aminophylline, as well as use of an ipratroprium bromide inhaler and 100% oxygen by mask. He was discharged to the ward, and continued on prednisone (deltacortisone), beclomethasone inhaler, ipratroprium inhaler, and salbutamol inhaler. During his ICU stay, he complained of nonspecific abdominal pain, interpreted as gastro-oesophageal reflux. After four days, he was discharged to the ward. On his sixth hospital day, he began to experience right-sided lower abdominal pain and right shoulder pain. A surgeon was consulted, and the patient was found to have a very tender right lower quadrant with guarding and rebound pain. He was therefore scheduled for appendicectomy; antibiotic therapy with ampicillin, gentamicin, and metronidazole was initiated.     

Propofol sequestration within the extracorporeal circuit

Various drugs administered during cardiac anaesthesia are sequestered in the extracorporeal circuit in vitro, but it is uncertain whether this sequestration phenomenon affects plasma drug concentration in vivo. The present study was undertaken to evaluate (1) in vitro sequestration of propofol in the extracorporeal circuit and (2) whether the change in plasma propofol concentration induced by initiation of cardiopulmonary bypass in vivo can be explained by haemodilution. For the in vitro evaluation, three separate experiments with a closed circuit (membrane oxygenator, reservoir, and tubings) were performed. The pH and PCO₂ of the circulating solution (a mixture of Ringer’s acetate and whole blood) were maintained within the normal physiological range, and the temperature of the solution was 28° C. The solution was circulated at a flow of 4 L · min^?1 and propofol was added to the solution to achieve a concentration of 2 μg · ml^?1. Serial samples were taken from the circulating solution for measurement of propofol concentration by high performance liquid chromatography. In the in vivo part of the study, 14 patients received a continuous infusion of propofol, and samples for the determination of plasma propofol concentration and blood haematocrit were taken before and five and ten minutes after initiation of cardiopulmonary bypass. In vitro, at 5 and 120 min after addition of propofol into the circulating solution, approximately 65% and 25%, respectively, of the predicted propofol level was measurable in the solution. In vivo, five minutes after initiation of the cardiopulmonary bypass plasma propofol concentration decreased (P < 0.001) more (from 2.8 ±0.7 (mean ± SD) to 1.5 ± 0.5 μg · ml^?1, a 45 ± 12% decrease) than would have been predicted on the basis of acute haemodilution (a decrease in haematocrit from 0.39 ± 0.04 to 0.28 ± 0.03 is a 29 ± 4% decrease). Ten minutes after initiation of cardiopulmonary bypass, plasma propofol concentration was 1.6 ± 0.5 μg · ml^?1 (a 37 ± 27% decrease from the pre-bypass level) and haematocrit was 0.27 ± 0.04 (a 30 ± 6% decrease): the decrease in plasma propofol concentration was not different from the decrease observed in the haematocrit. In conclusion, propofol is markedly sequestered within the extracorporeal circuit in vitro. This sequestration may, to some extent, affect plasma propofol concentration in vivo.