NON-INVASIVE MEASUREMENT OF CARDIAC OUTPUT DURING INDUCTION OF ANAESTHESIA AND TRACHEAL INTUBATION: THIOPENTONE AND PROPOFOL COMPARED

We have investigated the haemodynamic changes in response toinduction of anaesthesia and tracheal intubation in patientswho received either thiopentone 5 mg kg^–1 or propofol3 mg kg^–1 followed by atracurium 0.5 mg kg^–1 andfentanyl 1.5 µg kg^–1. Anaesthesia was maintainedwith 0.6% enflurane and 50% nitrous oxide in oxygen with assistedventilation. Cardiac output and heart rate (HR) were monitoredcontinuously with a transthoracic impedence monitor. Mean HRdid not change after induction in each group, but increasedafter tracheal intubation in both groups (P < 0.01). Meancardiac index (CI) decreased after induction (P < 0.05) anddecreased further after tracheal intubation in both groups (P< 0.05). There was no difference between the two groups withrespect to changes in CI and HR. Mean arterial pressure (MAP)and systemic vascular resistance (SVR) did not change significantlyafter induction in the thiopentone group. Both variables increasedfrom preinduction values 1 min after tracheal intubation (P< 0.001). In contrast, both MAP and SVR decreased after inductionin the propofol group (P < 0.001) and did not differ frompreinduction values 1 min after tracheal intubation. MAP andSVR were greater in the thiopentone group compared with thepropofol group after induction and tracheal intubation (P <0.01).     

DEXMEDETOMIDINE ATTENUATES SYMPATHOADRENAL RESPONSES TO TRACHEAL INTUBATION AND REDUCES THE NEED FOR THIOPENTONE AND PEROPERATIVE FENTANYL

The effects of the new, highly selective alpha₂-adrenergic agonist,dexmedetomidine, were studied in a randomized, placebo-controlled,double-blind trial in 24 ASA I patients. Dexmedetomidine 0.6µg kg^–1 or saline was given i.v. 10 min before inductionof anaesthesia. The required dose of thiopentone was significantly(P < 0.001) smaller in the dexmedetomidine group (mean 4.4(SD 0.9) mg kg^–1) than in the control group (6.9 (1.6)mg kg^–1), and the drug attenuated the cardiovascular responsesto laryngoscopy and tracheal intubation. The concentration ofnoradrenaline in mixed venous plasma was smaller in the dexmedetomidinegroup during all phases of induction (P < 0.01). During surgery,fentanyl was required in a dose of 0.5 (0.6) mg kg^–1 and2.8(2.6) mg kg^–1 in the dexmedetomidine and control groups,respectively (P < 0.001). During 2h postoperative follow-up,oxycodone 0.06 (0.06) mg kg^–1 and 0.16 (0.1) mg kg^–1(P < 0.05) was given to the two groups respectively.     

INFLUENCE OF CROHN'S DISEASE ON THE PHARMACOKINETICS AND PHARMACODYNAMICS OF ALFENTANIL

We have compared the dose requirements, pharma cokinetics andpharmacodynamics of alfentanil in 12 patients with Crohn's diseaseand 10 control patients undergoing abdominal surgery. Plasmaconcentrations of ₁-acid glycoprotein (AAG) and alfentanil proteinbinding were also measured. Anaesthesia was induced with aifentanil100 µg kg^–1 and thiopentone, and maintained withnitrous oxide in oxygen and aifentanil 25–200 µgkg^–1 h^–1 Arterial blood samples were obtained beforeand after each change in the aifentanil infusion rate and for6 h after stopping the infusion. Pharmacokinetic data were derivedusing non-compartmental methods. Alfentanil concen tration—effectdata were evaluated by non-linear regression, where effect waseither response or no response to surgical stimulation. Meanintra operative aifentanil requirement was greater in patientswith Crohn's disease (2.48 µg kg^–1 min^–1)than in control patients (1.35 µg kg^–1 min^–1)(P< 0.01). Mean elimination half-life, total plasma clearanceand steady state distribution volume in patients with Crohn'sdisease were comparable to those in control patients (80 vs81 min, 5.7 vs 6.4 ml kg^–1 min^–1 and 0.70 vs 0.68litre kg^–1, respectively). Mean plasma concentration atwhich the probability of no response was 50% for the intra-abdominalperiod of surgery was greater in the Crohn group (359 ng ml^–1)than in the control group (199 ng ml^–1 (P<0.02). PlasmaAAG concentrations were greater in the Crohn group, but thefree fraction of aifentanil was similar in both groups. Thisstudy indicates that the increased alfentanil requirement inpatients with Crohn's disease may be attributed to a changein pharmacodynamics. (Br. J. Anaesth. 1993; 71: 827–834)     

EFFECTS OF PINDOLOL ON THE CARDIOVASCULAR RESPONSE TO TRACHEAL INTUBATION

Laryngoscopy and tracheal intubation often cause hypertensionand tachycardia, which may be exaggerated during rapid-sequnceinduction of anaesthesia.We was studied the efficacy pindololin attenuating the cardiiovascular responses to laryngoscopyand intubation in patients receiving pindolol 2 µg kg^–1or 4 µg g^–1 min before induction of anaesthesiain a double-blind design. The data were compared with thosefor a control group receiving saline. Each group consisted of10 patients undergoing elective surgery. Anaesthesia was inducedwith thiopentone 5 mg kg^–1 i.v. and trachea/intubationwas facilitated with vecuronium 0.2mg kg^–1 Patients receivingsaline showed a significant increase in mean arterial pressureand heart rate associated with tracheal intubation. These increasesafter tracheal intubation were reduced in pindolol 4 4 4 µgkg^–-1 treated patients compared with those of the controlgroup (P<0.05). Pindolol 2 µg kg^–1 attenuatedtachycardia in response to intubation but did not afftect hypertension.These data suggest that a bolus injection of pindololµg4 kg^–-1 is a simple, practical and effective method foratenuating cardiovascular responses to laryngoscopy and trachealintubation.     

EFFECT OF ANAESTHESIA WITH NITROUS OXIDE IN OXYGEN AND FENTANYL ON RENAL FUNCTION IN THE ARTIFICIALLY VENTILATED DOG

The effect on renal function of a large dose (25 µg kg^–1)of fentanyl was investigated in 10 labrador dogs. The animalswere anaesthetized with nitrous oxide in oxygen and a smallsupplement of fentanyl 0.4 µg min^–1 throughout theexperiment, and muscular relaxation was provided by alcuronium,pulmonary ventilation being controlled. In the initial phaseof each experiment, estimated renal plasma flow, glomerularfiltration rate, urine volume, mean arterial pressure and renalvascular resistance were measured at 30-min intervals, threesets of samples being taken. Then the large dose of fentanylwas given over a 10-min period and the measurements were repeatedat 30-min intervals for 90 min. Changes in renal function lastedfor about 90 min; there was a significant decrease in estimatedrenal plasma flow (P< 0.01), glomerular filtration rate (P<0.001), urine volume (P<0.01) and mean arterial pressure(P< 0.001) together with an increase in renal vascular resistance(0.05>>P > 0.02). These changes were accompanied bybradycardia, but were still present when atropine was given.     

CARDIAC EFFECTS OF ATROPINE AND GALLAMINE IN PATIENTS RECEIVING SUXAMETHONIUM

Eighty healthy patients were randomly allocated to four groups.Atropine 0.01 mg kg^–1 i.v. (group I), gallamine 0.3 mgkg^–1 i.v. (group II), atropine 0.01 mg kg^–1 i.m.and gallamine 0.3 mg kg^–1 i.v. (group III), or atropine0.01 mg kg^–1 i.v. and gallamine 0.3 mg Lrg^–1 i.v.(group IV) were given before operation. After induction of anaesthesiawith thiopentone, suxamethonium 1 mg kg^–1 was given i.v.The lungs were ventilated with halothane in nitrus oxide inoxygen. Five minutes later the same dose of suxamrthonium wasrepeated. E.c.g. was monitored continuously. No serious bradycardiawas observed following a second injection of suxamethonium inany group. The results suggest that thiopentone protects againstsuxamethonium-induced bradycardia during halothane anaesthesia.     

INFLUENCE OF PREMEDICATION ON PLASMA ACTH AND CORTISOL CONCENTRATIONS IN CHILDREN DURING ADENOIDECTOMY

The endocrine response to stress, as reflected by the plasmaconcentrations of ACTH and cortisol, was investigated in 14children receiving two different premedications during halothaneanaesthesia for adenoidectomy. Seven children (group A) werepremedicated with diazepam 5mg rectally and atropine 0.3–0.4mgsublingually and seven (group B) received a rectal combinationof diazepam O.5mgkg^–1, morphine 0 15mgkg^–1 and hyoscine0.01 mg kg^–1. Before and after surgery plasma concentrationsof ACTH and cortisol were lower in group B than in group A.In group A mean values for ACTH increased from 4O.7nglitre^–1before adenoidectomy to 352.9 nglitre^–1 (P<0.001) afteradenoidectomy. The corresponding increase in group B was from12.1 nglitre^–1 to 82.1 nglitre^–1 (P<0.01). Ingroup A mean cortisol concentrations increased from 235.7 nmollitre^–1 to 655.7 nmol litre^–1 after adenoidectomy(P< 0.001) and in group B from 121.4 nmol litre^–1 to427.9nmol litre^–1 (P<0.01). End-tidal carbon dioxidetension was approximately the same in both groups. It was concludedthat the combination of diazepam, morphine and hyoscine decreasedthe endocrine response to stress     

COMPARISON OF CNS EFFECTS OF PROPOFOL AND THIOPENTONE IN CATS

Using cats with chronically implanted brain electrodes, we havecompared the effects of propofol on CNS electrical activitieswith those of thiopentone. Ten cats were allocated to receiveeither propofol (n = 5) or thiopentone (n = 5). Cats were anaesthetizedinitially with 4% halothane in oxygen. The trachea was intubatedand the lungs ventilated mechanically. A femoral artery anda vein in a forepaw were cannulated for arterial pressure monitoringand fluid infusion. After the inspired concentration of halothanewas maintained at 0.5%, EEG in the cortex, the amygdala andthe hippocampus, somatosensory evoked potential (SEP) and reticularmulti-unit activity (R-MUA) were recorded. Incremental dosesof propofol or thiopentone were administered i. v. at 5-minintervals during 0.5% halothane anaesthesia. The cumulativedoses of propofol and thiopentone were 2, 5, 10 and 20mg kg^–1,and 4, 10, 20 and 40 mg kg^–1 respectively. Arterial pressurewas maintained in excess of 100 mm Hg systolic by infusion ofphenylephrine. All cats in the propofol group survived, buttwo in the thiopentone group died after the adminstration ofthiopentone 40mg kg^–1 Changes observed in CNS activitywere dose-related in all cases. The EEG changed with the incrementsof doses of propofol or thiopentone, from fast, small amplitudeto complexes of fast and slow, large amplitude activities, burstsuppression and flat EEG. SEP latency was prolonged by bothagents: the peak latency of N1 changed from 15 (SD 2) ms to20 (5) ms with propofol 20mg kg^–1, and from 14 (1) msto 27(2) ms with thiopentone 40 mg kg^–1. SEP amplitudeswere depressed by both agents: the amplitude of N1 was depressedby 70 (29) % with propofol 20 mg kg^–1 and by 60 (33) %with thiopentone 40mg kg^–1. The R-MUA also was depressedby both agents: 85 (4) % with propofol 20 mg kg^–1 and85 (8) % with thiopentone 40mg kg^–1. The R-MUA was depressedto 50% of control by propofol 3.2 (1.6) mg kg^–1 or thiopentone6.7 (5.0) mg kg^–1. These depressive actions on the EEG,SEP and R-MUA induced by propofol were similar to those inducedby twice the equivalent doses of thiopentone on an mg kg^–1basis. These results indicate that propofol has the same simpledepressant effects as thiopentone on CNS electrical activity.     

COMPARISON OF THE INDUCTION CHARACTERISTICS OF THIOPENTONE AND PROPOFOL IN CHILDREN

The induction characteristics of propofol 2.0–2.5 mg kg^–1were compared with those of thiopentone 4–5 mg kg^–1in 60 fit children aged between 3 and 16 yr. All patients receivedi.m. premedication with papaveretum 0.4 mg kg^–1 (maximumdose 15 mg) and hyoscine 0.008mg kg^–1 (maximum dose 0.3mg). Seven children (24%) complained of pain after injectionwith propofol, compared with three (10%) after thiopentone.No child ir either group complained of severe pain. Excitatoryeffects were observed in 10 children (33%) receiving propofolas opposed to five children (16%) after thiopentone, but thesewere transient and minor and all occurred after completion ofinjection. Apnoea lasting longer than 30 s occurred in onlyfour children (13%) in each group despite the use of opioidpremedication. The mean duration of apnoea was similar in bothgroups. Propofol caused greater decreases in arterial pressures(systolic, diastolic, mean) than thiopentone, but only the differencein systolic arterial pressure achieved significance. There wasa significant difference in heart rate, which did not changeafter propofol, but increased with thiopentone. The overallquality of induction was assessed as being good in all childrenreceiving thiopentone compared with 20 (66%) of those receivingpropofol.     

PROPOFOL FOR INDUCTION AND MAINTENANCE OF ANAESTHESIA: COMPARISON BETWEEN YOUNGER AND OLDER PATIENTS

The propofol requirements for the induction and maintenanceof anaesthesia were compared in groups of younger and olderpatients. Side effects, influence on the cardiovascular systemand recovery times were compared between 20 unpremedicated ASAI–III, 25–40-yr-old patients and 20 65–80-yr-oldpatients all scheduled to undergo elective surgery. After inductionwith propofol, anaesthesia was maintained with a continuousinfusion of the drug. Vecuronium and fentanyl were administeredas required. In the young group propofol 2.2 mg kg^–1 andin the elderly 1.7 mg kg^–1 were needed for induction (P< 0.05). The maintenance doses were 10.0 mg kg^–1 h^–1and 8.6 mg kg^–1 h^–1, respectively (P < 0.01).Side effects were more pronounced in the younger patients. Influenceson the cardiovascular system were definite, but mild. The youngerpatients awoke sooner: 7.8 v. 14.3 min (P < 0.01) after thediscontinuation of the infusion of propofol.     

Reducing stress responses in the pre-bypass phase of open heart surgery in infants and young children: a comparison of different fentanyl doses

High-dose opioids are advocated for paediatric cardiac surgeryto suppress stress responses but they can produce unwanted sideeffects. There are no data on the dose-dependent effects ofopioids on the stress response on which to base rational opioidadministration. We conducted a dose ranging study on 40 childrenless than 4 yr undergoing elective open heart surgery usingone of five fentanyl doses: 2, 25, 50, 100 or 150 µg kg^–1before surgery. The standardized anaesthetic also included pancuroniumand isoflurane. Blood samples were taken at induction, beforeincision, after sternotomy, immediately before, and at the endof cardiopulmonary bypass. Patients in the 2 µg kg^–1group had significant rises in pre-bypass glucose (P<0.01),pre- and post-bypass cortisol (P<0.01), and pre- and post-bypassnorepinephrine (P<0.01). No significant rise occurred inglucose, cortisol and catecholamines in any of the higher dosagegroups. Patients in the 2 µg kg^–1 group had significantlyhigher mean systolic blood pressure (P<0.02) and heart rate(P<0.04). A balanced anaesthetic containing fentanyl 25–50µg kg^–1 is sufficient to obtund haemodynamic andstress responses to the pre-bypass phase of surgery. Higherdoses of fentanyl (100 and 150 µg kg^–1) offer littleadvantage over 50 µg kg^–1, and can necessitate interventionto prevent hypotension.     

USE OF AN EMULSION OF ICI 35868 (PROPOFOL) FOR THE INDUCTION AND MAINTENANCE OF ANAESTHESIA

2,6-Diisopropyl phenol in a fat emulsion formulation (propofol)has been used to supplement 67% nitrous oxide in oxygen anaesthesiain 20 patients premedicated with morphine 0.15 mg kg^-1and atropine0.6 mg, and undergoing body surface surgery. Following an inductiondose of propofol 2.5 mg kg^-1, the mean maintenance dose was73.4µg kg^-1min^-1. When compared with 10 patients receivingAlthesin to supplement nitrous oxide in oxygen in a similarmanner, recovery was considerably faster following propofol.The only major side-effect associated with the use of propofolwas pain on injection in nine out of 20 patients. When the patientsreceiving propofol were compared with a second control group(n = 11) in whom anaesthesia was induced with thiopentone 4mg kg^-1and maintained with 1 % halothane and nitrous oxide inoxygen, the former group showed a significant (P<0.01) decreasein the plasma cortisol concentration 30 min after the inductionof anaesthesia. However, by 3 h after induction, the cortisolconcentration in both groups was not significantly differentfrom the baseline (pre-induction) value. The mechanism of thisdecrease is not known. In vestigation of the influence of thefat emulsion on blood coagulation andfibrinolysis revealed nodifferences when compared with patients receiving Althesin.     

DOSE-RESPONSE RELATIONSHIPS FOR EDROPHONIUM AND NEOSTIGMINE ANTAGONISM OF MIVACURIUM-INDUCED NEUROMUSCULAR BLOCK

We have studied the dose-response relationships for neostigmineand edrophonium during antagonism of neuromuscular block inducedby mivacurium chloride. Sixty-four ASA group I or II adultswere given mivacurium 0.15 mg kg^–1 during fentanyl-thiopentone-nitrousoxide-iso flurane anaesthesia. Train-of-four stimulation (TOF)was applied to the ulnar nerve every 10 s, and the force ofcontraction of the adductor pollicis muscle was recorded. Whenspontaneous recovery of first twitch height reached 10% of itsinitial control value, edrophonium 0.1, 0.2, 0.4, or 1 mg kg^–1or neostigmine 0.005, 0.01, 0.02, or 0.05 mg kg^–1 wasadministered by random allocation. Neuromuscular function inanother 16 subjects was allowed to recover spontaneously. Spontaneousrecovery from 90% mivacurium block to 95% twitch height andTOF ratio 0.75 occurred within 15 min. This study demonstratedthat the dose-response curves for these two drugs for antagonismof neuromuscular block (first twitch and train-of-four ratio)were parallel. The doses of neostigmine required to achieve50% (ED₅₀) and 70% (ED₇₀) recovery of the first twitch after10 min were 2 (1.5– 2.5) µg kg^–1 and 4.7 (4.1–5.4)µg kg^–1 (mean (95% confidence intervals)), respectively.Corresponding ED₅₀ and ED₇₀ values for edrophonium were 2.8(0.75–10.2) pg kg^–1 and 9.2 (3.6–23.6) µgkg^–1, respectively. These values corresponded to neostigmine:edrophonium potency ratios of 1.4 (0.4–2.4) and 1.95(0.9–2.9) for first twitch ED₅₀ and ED₇₀ height, respectively.The calculated doses producing 50% (ED₅₀ recovery of the TOFratio at 10 min were neostigmine 2.57 (1.8–3.6) µgkg^–1 and edrophonium 26.9 (14.6–49.6) pg kg^–1.These values corresponded to a potency ratio of 10.4 (0.7–20).(Br. J. Anaesth. 1993; 71: 709–714)     

HAEMODYNAMIC CHANGES AFTER INDUCTION OF ANAESTHESIA AND TRACHEAL INTUBATION FOLLOWING PROPOFOL OR THIOPENTONE IN PATIENTS OF ASA GRADE I AND III

Thirty-six ASA I patients received either propofol 2.25 (0.07)mg kg^–1 (mean (SEM)) or thiopentone 4.8 (0.18) mg kg^–1,for induction of general anaesthesia together with fentanyland a neuromuscular blocking drug. This technique was repeatedin 12 ASA III patients, using propofol 1.8 (0.18) mg kg^–1or thiopentone 4.7 (0.37) mg kg^–1. There was a significantdecrease in systolic arterial pressure following induction ofanaesthesia with both drugs; this was more pronounced afterpropofol, and in ASA III patients. Plasma noradrenaline concentrationsincreased after tracheal intubation only in the thiopentonegroup, but the pressor response to tracheal intubation was notattenuated by the use of propofol.     

EFFECT OF COMPETITIVE MYONEURAL BLOCKADE AND FENTANYL ON MUSCLE FASCICULATIONS CAUSED BY SUXAMETHONIUM IN CHILDREN

The effects of tubocurarine 0.06mg kg^–1, alcuronium 0.03mg kg^–1, pancuronium 0.01 mg kg^–1, and fentanyl1 or 2 µg kg^–1 on the muscle fasciculations associatedwith suxamethonium were studied in 171 children undergoing otolaryngologicalsurgery. The mean fasciculation index in all pretreatment groupswas significantly smaller than in the control group. The mosteffective pretreatment was fentanyl 2µg kg^–1 followed,in order, by alcuronium, fentanyl 1 µg kg^–1, tubocurarineand pancuronium. The rate of the onset of the fasciculationsafter the injection of suxamethonium ranged from 8 s after pancuroniumto 20 s after tubocurarine. There was evidence of respiratorydepression in the children receiving fentanyl 2 µg kg^–1if the duration of anaesthesia was less than 30 min.     

Comparison of intubating conditions following propofol and succinylcholine with propofol and remifentanil 2 micrograms kg-1 or 4 micrograms kg-1

We evaluated the intubating conditions, haemodynamic responsesand duration of apnoea in 60 healthy adult patients after propofol2 mg kg^–1 combined with either a bolus of remifentanil2 µg kg^–1 or 4 µg kg^–1,or succinylcholine 1 mg kg^–1. Patients intubatedfollowing remifentanil showed dose-dependent intubating conditions,similar at 4 µg kg^–1 to the conditionsproduced with succinylcholine. Post-induction mean arterialpressure decreased from baseline values by 21% (P<0.0001),28% (P<0.0001) and 8% (P>0.05) in the remifentanil 2 µg kg^–1,remifentanil 4 µg kg^–1 and succinylcholine1 mg kg^–1 groups, respectively. The mean (SD)duration of apnoea following induction was 9.3 (2.6) minand 12.8 (2.9) min in the remifentanil 2 µg kg^–1and 4 µg kg^–1 groups, and 6.0 (0.9) minin the succinylcholine group (P<0.001 between groups). Br J Anaesth 2000; 85: 623--5     

PREVENTION OF INTRACRANIAL HYPERTENSION DURING LARYNGOSCOPY AND ENDOTRACHEAL INTUBATION: Use of a second dose of thiopentone

In nine patients, with preoperative ICP monitoring, anaesthesiawas induced with thiopentone 5 mg kg^–1 given over 1 min,followed by pancuronium 0.l mg kg^–1. After manual hyperventilationwith nitrous oxide and oxygen for 3 min they were given thiopentone2.5 mg kg^–1 over 30 s (phase 1); 30 s later laryngoscopywas performed and topical analgesia administered to the larynx.Endotracheal intubation was performed 1 min after spraying thecords (phase 2). The measurements continued for a further 5min during which the patients were mechanically ventilated (phase3). ICP and intra-arterial pressure were recorded. Althoughthere was a significant decrease (P<0.05) in MAP at the endof the second dose of thiopentone, there were no other significantchanges in ICP, MAP or Pa_CO2 throughout the study. In two patientsthere were transient decreases in cerebral perfusion pressureto less than 60 mm Hg. Although MAP increased in five of thepatients during laryngoscopy and intubation, there was no increasein ICP, showing that the MAP was still within the autoregulatorylimits     

COMPARISON OF DIAZEPAM AND FLUNITRAZEPAM FOR SEDATION DURING LOCAL ANAESTHESIA FOR BRONCHOSCOPY

Diazepam and flunitrazepam were compared as amnesic and sedativeadjuncts to local anaesthesia for diagnostic bronchoscopy in92 patients. After local anaesthesia of the pharynx, larynxand trachea with lignocaine, atropine plus diazepam or flunitrazepamwas injected i.v. The co-operation of the patients and the technicalcircumstances under which the bronchoscopy was performed weregood in each group. None of the treatments significantly modifiedarterial pressure or heart rate. Two hours after the injection,flunitrazepam 0.01 mg kg^–11 more frequently caused amnesiafor pictures shown to the patients during the first 15 min afterinjection (failure to recall 42–75%, and for bronchoscopy67%), than did diazepam 0.125 mg kg^–11 (failure to recall21–67%; bronchoscopy 38%). Double doses of the drugs causedamnesic actions similar to those of flunitrazepam 0.01 mg kg^–11.When failure to recall was assessed on the following day, 29%and 5% of the patients remembered bronchoscopy after flunitrazepam0.01 and 0.02 mg kg-1 respectively; after diazepam 0.125 and0.25 mg kg^–11 the corresponding percentages was 59% and30% (P<0.05 v. flunitrazepam). The ability to stand and walkon a straight line was similar after the smaller doses of bothdrugs, but after the larger doses recovery was slower afterflunitrazepam. Psychomotor performance was still distinctlyimpaired 2 h after the injection of the larger doses.     

BLOOD CYANIDE AND THIOCYANATE CONCENTRATIONS PRODUCED BY LONG-TERM THERAPY WITH SODIUM NITROPRUSSIDE

Blood cyanide (HCN) or plasma thiocyanate (SCN) concentrations,or both, were measured in 30 patients (ages 11 months-72 yr)receiving sodium nitroprusside (SNP) for 12–314 h. Sequentialmeasurements in three of these patients (infused 5, 12 and 13days) showed that HCN concentrations varied with dose rate,while SCN concentrations increased linearly with increasingSNP dose. The accumulated data confirmed that the rate of administration(0.3–6.5 µg kg^–1 min^–1) determined theplasma HCN concentrations (0–3.8 µmol litre^–1;y = 0.267 x - 0.0733; r = 0.64; n = 51; P< 0.001). Thus,if prolonged exposure to plasma HCN concentrations greater than1 µmol litre^–1 is to be avoided, the maximum safesustained dose rate of SNP will lie near to 4 µg kg^–1min^–1. Likewise, the SCN results (30—880 iimol litre^–1)confirmed the close relationship between plasma concentrationsand the total SNP dose (0.44–32.9 mg kg^–1; y = 24.6x+ 74.9; r = 0.95, n = 51, P < 0.001). Therefore, we suggestthat, to avoid SCN toxicity (plasma SCN > 1.75 µmollitre^–1), in the absence of SCN monitoring, the totalSNP dose should be less than 70 mg kg^–1 in patients withnormal renal function.     

COMPARISON OF THE CARDIOVASCULAR EFFECTS OF BOLUS V. INCREMENTAL ADMINISTRATION OF THIOPENTONE

Twenty unpremedicated patients (ASA grade I) were assigned randomlyto receive thiopentone in 50-mg increments every 15 s untilloss of lash reflex (group I) or as a 4-mg kg^–1 bolus(group II). Arterial pressure, heart rate, systolic time intervalsand end-tidal carbon dioxide were measured in the control stateand then every 30 s. The mean dose of thiopentone in group Iwas 5.58±1.24 (SD) mg kg^–1 which was significantlylarger than in group II (P< 0.001). Both groups exhibitedsimilar decreases in arterial pressure and increases in heartrates. The degree of cardiac depression revealed from measurementof the systolic time intervals, indexed for heart rate, wasequal in the two groups.