Effect of sympathomimetic drugs and corresponding receptor antagonists on the rate of cerebrospinal fluid production.

The bulk production of cerebrospinal fluid (CSF) was measured in rabbits on the basis of ventriculocisternal perfusion and dilution of [¹⁴C]inulin. Intraventricular or intravenous (i.v.) infusion of norepinephrine produced a dose-related decrease in the production by as much as 50%, the effect being counteracted by both α- and β-antagonists (except when the latter was given i.v., which potentiated the i.v. norepinephrine response). Also intraventricular (but not i.v.) administration of the β₁-receptor agonist, $\text{H80}\text{62}$, reduced CSF formation (effect blocked by practolol), in contrast to the β₂ agonist, terbutaline, which had little or no effect. It is suggested that the sympathomimetic reduction in the rate of CSF formation is the result of a combined β₁-receptor-mediated inhibition of the secretion from the plexus epithelium and a reduced blood flow in the tissue resulting from stimulation of the vascular α-receptors.     

Acanthocytosis associated with tics and involuntary movements

Summary A resume of the clinical features presented in the 3 families previously reported with acanthocytosis and normolipoproteinaemia is presented and particular attention paid to the nature of the oro-facial dyskinetic movements seen.No defects were detected in the red cell membranes but a plasma abnormality, possibly related to the increased fibrinogen levels, was examined by study of the electrokinetic properties of the pathological platelet-plasma system. These results were compared with those of the pathological platelet-plasma system of a patient with abetalipoproteinaemia but no correlation was found.The link between the haematological and neurological abnormalities in the acanthocytotic syndromes has yet to be discovered.     

Hallervorden-spatz disease—Late infantile and adult types,report of two cases

Summary Two cases of Hallervorden-Spatz disease are reported, one of whom was a late infantile variety and the other an adult variety who died at the end of the fourth decade of life. The clinical and neuropathological aspects were similar to previously reported cases. Both cases were characterized by a slowly progressive illness featured by dementia, seizures, dysarthria, rigidity, spasticity and athetoid and myoclonic movements. Neuropathological examination disclosed excessive pigmentation of the globus pallidus and red zone of substantia nigra associated with neuroaxonal dystrophy. The latter was more generalized in the first case and was confined to the pallidonigral area, cerebellum and lower medulla in the adult case.In spite of a striking increase in the iron content of the pallidonigral system, as demonstrable by histological techniques, the chemical analysis disclosed only slight rise of iron in this area. There was a generalized reduction of cerebral lipids compatible with a diffuse degenerative process associated with demyelination.Our sincere thanks are due to Dr.G. A. Ives, the Director of the Yorkton Psychiatric Centre, and to Dr.N. L. Hoffmann, the Pathologist of Regina General Hospital, for the brain specimens, general pathological report and the clinical notes of the two cases. Dr.J. Horbaczewski of the Saskatchewan Hospital, Weyburn, made available for us the files of the patient W.D. The technical assistance of Mrs.N. Nebeluk, R.T., and that of Mr.H. Goodwin and Mr.R. C. Shortman is gratefully acknowledged.     

Effect of fluid loading with saline or colloids on pulmonary permeability, oedema and lung injury score after cardiac and major vascular surgery

Background. The optimal type of fluid for treating hypovolaemiawithout evoking pulmonary oedema is still unclear, particularlyin the presence of pulmonary vascular injury, as may occur aftercardiac and major vascular surgery. Methods. In a single-centre, prospective, single-blinded clinicaltrial 67 mechanically ventilated patients were randomly assignedto receive saline, gelatin 4%, HES 6% or albumin 5%, accordingto a 90 min fluid loading protocol with target central venouspressure of 13 and pulmonary capillary wedge pressure of 15mm Hg, within 3 h after cardiac or major vascular surgery. Beforeand after the protocol, we recorded haemodynamics and ventilatoryvariables and took chest radiographs. The pulmonary vascularinjury was evaluated using the ⁶⁷Ga-transferrin pulmonary leakindex (PLI) and extravascular lung water (EVLW). Plasma colloidosmotic pressure (COP) was determined and the lung injury score(LIS) was calculated. Results. More saline was infused than colloid solutions (P<0.005).The COP increased in the colloid groups and decreased in patientsreceiving saline. Cardiac output increased more in the colloidgroups. At baseline, PLI and EVLW were above normal in 60 and30% of the patients, with no changes after fluid loading, exceptfor a greater PLI decrease in HES than in gelatin-loaded patients.The oxygenation ratio improved in all groups. In the colloidgroups, the LIS increased, because of a decrease in total respiratorycompliance, probably associated with an increase in intrathoracicplasma volume. Conclusions. Provided that fluid overloading is prevented, thetype of fluid used for volume loading does not affect pulmonarypermeability and oedema, in patients with acute lung injuryafter cardiac or major vascular surgery, except for HES thatmay ameliorate increased permeability. During fluid loading,changes in LIS (and respiratory compliance) do not representchanges in pulmonary permeability or oedema.      

Propofol metabolism is enhanced after repetitive ketamine administration in rats: the role of cytochrome P-450 2B induction

Background. In a series of ex vivo and in vivo studies we investigatedthe ability of repetitive ketamine administration to alter themetabolism and anaesthetic effect of propofol and the role ofketamine-mediated P-450 2B induction in rats. Methods. Male Wistar rats were pretreated with 80 mg kg^–1ketamine i.p. twice daily for 4 days. Pentoxyresorufin O-dealkylation(PROD), P-450 2B protein and mRNA were determined. Residualpropofol concentration was measured after incubating hepaticmicrosomes with 100 µM propofol. Sleeping times inducedby i.p. 80 mg kg^–1 propofol were determined. Orphenadrine,a P-450 2B inhibitor, was added in both ex vivo and in vivostudies. Finally, serial whole blood propofol concentrationswere determined after i.v. infusion of 15 mg kg^–1 propofol. Results. Ketamine pretreatment produced 5.4-, 3.4- and 1.7-foldincreases in hepatic PROD activity, P-450 2B protein and mRNA,respectively. Residual propofol concentration was 46% lowerafter incubation with microsomes from ketamine-pretreated ratsthan in the control group. The addition of orphenadrine to ketamine-pretreatedmicrosomes produced an increase in residual propofol concentrationin a concentration-dependent manner. Ketamine pretreatment reducedpropofol sleeping time to 12% of the control, which was reversedby orphenadrine. The whole blood propofol concentration in ketamine-pretreatedrats was significantly lower than that of control rats at 1,2, 4 and 8 min after cessation of propofol infusion. Conclusions. Repetitive ketamine administration enhances propofolmetabolism and reduces propofol sleeping time in rats. We suggestthat P-450 2B induction may produce ketamine–propofolinteraction in anaesthetic practice.     

Skin conductance monitoring compared with Bispectral Index to assess emergence from total i.v. anaesthesia using propofol and remifentanil

Background. Arousal after sevoflurane anaesthesia has been detectableby monitoring changes in skin conductance (SC) with similaraccuracy as monitoring Bispectral Index (BIS^®). As SC monitoringdetects changes in sympathetic tone, the measurements mightbe confounded by the sympatholytic properties of propofol, acomponent of total i.v. anaesthesia (TIVA). Therefore in thisstudy, monitoring of SC during emergence from TIVA was comparedwith the monitoring of BIS^®. Methods. Twenty-five patients undergoing plastic surgery wereinvestigated. The number of fluctuations of SC per second (NFSC),BIS^® and haemodynamic variables [systolic blood pressure(SBP) and heart rate (HR)] were recorded simultaneously. Theperformance of the monitoring devices in distinguishing betweenthe clinical states ‘steady-state anaesthesia’,‘first clinical reaction’ and ‘extubation’were compared using the method of prediction probability (Pk)calculation. Results. BIS^® showed the best performance in distinguishingbetween ‘steady-state anaesthesia’ and ‘firstreaction’ (Pk BIS^® 0.99 vs NFSC 0.80; P<0.01),and ‘steady-state anaesthesia’ and ‘extubation’(Pk BIS^® 1.00 vs NFSC 0.91; P<0.05); the time from firstchange of BIS^® or NFSC to a first clinical reaction wassignificantly longer for NFSC (median BIS^® 135 s vs NFSC191 s; P<0.05). BIS^® and NFSC performed better in distinguishingbetween the investigated clinical states than SBP and HR. Conclusions. In this study, BIS^® was found to predict arousalwith a higher probability but slower response times than NFSCin patients waking after TIVA.     

Bispectral index is a topographically dependent variable in patients receiving propofol anaesthesia

Background. As very strong agreement has been reported betweenbispectral index (BIS) values measured from the occipital andfrontal skull areas, we compared BIS values measured from centraland parietal areas with those from frontal area to investigatewhether BIS is really a topographically dependent or topographicallyindependent variable. Methods. Twenty patients, ASA I–II, non-obese, aged 18–62yr and with no neurological disorders were enrolled. Based onthe 10–20 international landmarks, five silver dome electrodeswere positioned: F7, C3, P7, Cz (common reference) and Fp1 (ground).Using frontal (F7–Cz), central (C3–Cz) and parietal(P7–Cz) electrode montages, the corresponding BIS valueswere simultaneously recorded with an Aspect A-1000 monitor (softwarev3.12). The BIS values were recorded at the propofol concentrationallowing laryngeal mask insertion, which was maintained duringthe 10 min data collection period in absence of additional externalstimuli. Data were analysed using the Kruskall–Wallis,Wilcoxon paired sign with Bonferroni correction, Bland–Altmanand linear correlation tests. Results. At the predicted effect target propofol concentration4–8 µg ml^–1, the 10 min mean BIS (median [min–max])were 32 [20–44], 46 [28–68] and 58 [41–72]for the frontal, central and parietal leads, respectively. Differencesbetween these BIS recordings were statistically significant(P<0.0001, Kruskall–Wallis; P<0.005, Wilcoxon pairedsign test). Conclusions. The present results provide evidence that BIS indexis a topographically dependent variable in patients receivingpropofol anaesthesia.     

Effects of intraoperative i.v. acetaminophen vs i.m. meperidine on post-tonsillectomy pain in children

Background. Enteral acetaminophen, when used alone, is not veryeffective for postoperative analgesia because of delayed absorptionand sub-therapeutic plasma concentrations. In contrast, i.v.acetaminophen is devoid of these shortcomings and could potentiallyprovide adequate postoperative analgesia as a single agent.This randomized double-blind study compared the analgesic effectsof i.v. acetaminophen and i.m. meperidine in paediatric patientsundergoing tonsillectomy. Methods. Eighty children undergoing tonsillectomy were randomizedto receive either acetaminophen 15 mg kg^–1 i.v. (acetaminophengroup) or meperidine 1 mg kg^–1 i.m. (meperidine group),intraoperatively. Anaesthesia was induced with either sevofluraneinhalation or propofol, and was maintained with sevoflurane.After operation, the objective pain scale (OPS), Ramsay sedationscore and Aldrete score were recorded every 5 min, and nurses'satisfaction was determined on a 7-point scale (1–7). Results. On admission to the recovery room, OPS scores were3.1 (SEM 0.3) for the acetaminophen group and 2.1 (SEM 0.3)for the meperidine group (P=0.147); however, Ramsay sedationscores were 3 (SEM 0.2) and 4 (SEM 0.3) for the acetaminophenand meperidine groups, respectively (P<0.05). Patients inthe meperidine group continued to be more sedated 5 min afterarrival in recovery (P<0.05). Acetaminophen group patientsachieved an Aldrete score of 10 min sooner than those in themeperidine group [median (IQR) time: 15 (0–20) min vs25 (15–30) min, respectively, P=0.005]. Adjusted nursesatisfaction scores were similar in both groups [6.1 (SEM 0.2)vs 5.7 (SEM 0.2) min, P=0.311]. Conclusion. Compared with i.m. meperidine, i.v. acetaminophenprovided adequate analgesia, less sedation and earlier readinessfor recovery room discharge among paediatric patients undergoingtonsillectomy.     

Performing perioperative optimization of the high-risk surgical patient

Perioperative risk of death after general surgery is quotedas overall less than 1%. However, each individual's risk varieswidely according to many identified factors with some havinga significantly increased risk of a worse outcome. The observationthat manipulating and targeting certain physiological parametersin selected patients can influence this risk has been reportedin numerous studies. Yet it is still not widely practised toassist the process, despite the availability of various invasiveand non-invasive monitors. This may be in part because of alack of experience with the practicalities of perioperativeoptimization, and lack of knowledge in applying currently availabletools. This article aims to try and address this deficit andincrease awareness of how and when to utilize monitoring equipmentto achieve optimal results for the patients we treat.