Cerebrovascular response to carbon dioxide during sodium nitroprusside- and isoflurane-induced hypotension

We have examined the cerebrovascular response to carbon dioxideduring normotension, sodium nitroprusside (SNP)-induced hypotensionand high dose isoflurane-induced hypotension in 10 patientswho received a standardized general anaesthetic. Carbon dioxidereactivity was determined by varying Pa_co2 between 3.0 and 8.0kPa and recording simultaneously blood flow velocity from themiddle cerebral artery (vmca). The paired vmca-Pa_co2 data wereanalysed using linear regression to determine carbon dioxidereactivity. During hypotension, both high-dose isoflurane andSNP reduced significantly mean absolute (from 17.4 (SEM 2.3)to 13.0 (1.7) and 8.8 (1.3) cm s^–1 kPa^–1 respectively;P < 0.05) and relative (from 32.5 (3.8) to 23.6 (2.0) and15.5 (1.3) % kPa^– respectively; P < 0.05) cerebrovascularreactivity to carbon dioxide. This reduction was greater duringSNP-induced hypotension (P < 0.05). We conclude that cerebrovascularreactivity to carbon dioxide was attenuated during isofluraneand SNP-induced hypotension, and that it was better preservedduring isoflurane-induced hypotension. (Br. J. Anaesth. 1995;74: 296–300) Present addresses: Department of Anaesthesia, The Ipswich Hospital,Ipswich IP4 5PD, UK. Present addresses: Phoenix Anesthesia Group, 2950 North 7thSt, Phoenix, AZ 85014, USA. Present addresses: University of Basel/Kantonsspital, Departmentof Anesthesia, CH-4031, Basel, Switzerland.     

Cerebral haemodynamics in patients with chronic renal failure: effects of haemodialysis

Background. We measured middle cerebral artery (MCA) flow velocity(FV), dynamic pressure autoregulation, and carbon dioxide reactivity(CRCO₂) in patients with chronic renal failure before and afterhaemodialysis using transcranial Doppler ultrasonography. Methods. Twelve patients on long-term haemodialysis were recruited.MCA FV was measured continuously. The transient hyperaemic responsetest was used to assess cerebral autoregulation, and per centchange in FV per kPa change in end-tidal carbon dioxide wascalculated to assess CRCO₂. All measurements were recorded beforeand after haemodialysis. Results. MCA FV (mean [SD]) decreased from 57 (10) cm s^–1before to 46 (13) cm s^–1 after haemodialysis (P<0.01).The transient hyperaemic response ratio (THRR) was (mean [SD])1.29 (0.13) before haemodialysis and did not change significantlyfollowing haemodialysis (1.36 [0.10]). CRCO₂ was 21.7 (8.3)%kPa^–1 before haemodialysis and remained unchanged afterwards(20.9 [3.8]% kPa^–1). Values in normal subjects for MCAFV, THRR and CRCO₂ are 56 (12) cm s^–1, 1.26 (0.13) and22 (6)% kPa^–1, respectively. Conclusions. MCA FV decreases significantly after haemodialysis.Dynamic pressure autoregulation and CRCO₂ remain normal in patientswith chronic renal failure, and are not altered significantlyby haemodialysis. Presented at the European Society of Anaesthesiologists AnnualCongress Amsterdam, May 1999.     

CEREBROVASCULAR CARBON DIOXIDE REACTIVITY DURING EXPOSURE TO EQUIPOTENT ISOFLURANE AND ISOFLURANE IN NITROUS OXIDE ANAESTHESIA

We have studied the effects of hypocapnia on cerebrovascularchanges in two MAC-equivalent anaesthetic regimens, using thetranscranial Doppler technique as an index of cerebral bloodflow (CBF) in 24healthy ASA I patients undergoing spinal surgery.Eight of the patients were subjected to carbon dioxide reactivitychallenges in the awake state. Before surgery, the other 16patients received, in random order, either 1.15% isofluranein oxygen or 0.5% isoflurane with 70% nitrous oxide. Carbondioxide reactivity was calculated for each group as the increasein flow velocity per kPa change in PÉ_CO2 (cm s^–1kPa^–1). It was significantly greater for the isofluranegroup (14.09 (SD 2.44) cm s^–1 kPa^–1) and significantlyless for the isoflurane—nitrous oxide group (7.95 (1.32)cm s-^–1 kPa^–1) compared with the awake group (11.24(0.95) cm s^–1 kPa^–1). We conclude that cerebrovascularresponsiveness to changes in arterial carbon dioxide concentrationis influenced markedly by the anaesthetic procedure. Hyperventilationis more likely to affect CBF during isoflurane anaesthesia thanduring an MAC-equivalent isoflurane—nitrous oxide anaesthesia.     

Effect of 1 or 2 MAC isoflurane with or without ketanserin on cerebral blood flow autoregulation in man

We have studied the effect of 1 or 2 MAC isoflurane with orwithout ketanserin on cerebral blood flow (CBF), cerebral oxygenmetabolism (CMRO₂) and CBF autoregulation in 20 adult patientsundergoing lumbar disc surgery. Ten patients received ketanserinand 10 isotonic saline. CBF measurements were started after1 h of infusion of saline or ketanserin. The patients were anaesthetizedwith thiopentone 5 mg kg^–1 followed by isoflurane. During1 MAC of isoflurane, baseline values were recorded and thenCBF autoregulation was examined (mean arterial pressure increasedby about 30% with angiotensin). The sequence was repeated with2 MAC of isoflurane. CBF was measured by the i.v. xenon-133technique. CMRo₂ was calculated as the product of CBF and thecerebral arterio-venous oxygen content difference. Ketanserinhad no effect on CBF, CMRo² or CBF autoregulation during isofluraneanaesthesia, therefore all patients were pooled for evaluationof the effect of isoflurane. Increasing isoflurane anaesthesiafrom 1 to 2 MAC increased mean CBF from 41 to 49 ml /100 g min^–1(P<: 0.01) and decreased mean CMRo₂ from 1.5 to 1.1 ml/100g min^–1 (P < 0.001) and thus abolished the couplingbetween flow and metabolism. The CBF autoregulation test indicatedthat autoregulation was disrupted at 2 MAC, but not during 1MAC isoflurane anaesthesia. (Br. J. Anaesth. 1994; 72: 66–71)     

Effect of two anaesthetic regimens on airway nitric oxide production in horses

There is evidence that halothane inhibits nitric oxide synthasein vitro, but the effect of intravenous anaesthetic agents isless clear. This study was undertaken to compare the rate ofexhaled nitric oxide production (V_NO) in spontaneously breathinghorses anaesthetized with halothane or an intravenous regimen.Seven adult horses were studied twice in random order. Afterpremedication with romifidine 100 µg kg^–1,anaesthesia was induced with ketamine 2.2 mg kg^–1and maintained with halothane in oxygen (HA) or by an intravenousinfusion of ketamine, guaiphenesin and romifidine (IV). Inhaledand exhaled nitric oxide (NO) concentrations, respiratory minuteventilation (V_E), pulmonary artery pressure (P_PA), fractionalinspired oxygen concentration (FI_O2), end-tidal carbon dioxideconcentration (E'_CO2), cardiac output (Q) and partial pressuresof oxygen and carbon dioxide in arterial blood (Pa_O2, Pa_CO2)were measured. Exhaled nitric oxide production rate was significantlylower (40 min, P<0.01; 60 min, P<0.02) duringHA [40 min, 1.4 (SD 1.4) pmol l^–1 kg^–1 min^–1;60 min, 0.7 (0.7) pmol l^–1 kg^–1 min^–1]than during IV [40 min, 9.3 (9.9) pmol l^–1 kg^–1min^–1; 60 min, 12.5 (13.3) pmol l^–1 kg^–1min^–1). Mean pulmonary artery pressure was significantlyhigher (40 min, P<0.01; 60 min, P<0.001) during HA[40 min, 5.9 (1.1) kPa; 60 min, 5.9 (0.9) kPa] comparedwith IV (40 min, 4.4 (0.4) kPa; 60 min, 4.4 (0.5) kPa].NO is reduced in the exhalate of horses anaesthetized with halothanecompared with an intravenous regimen. It is suggested that increasedmean pulmonary artery pressure during halothane anaesthesiamay be linked to the differences in NO production. Br J Anaesth 2001; 86: 127–30     

DOSE REQUIREMENTS OF PROPOFOL BY INFUSION DURING NITROUS OXIDE ANAESTHESIA IN MAN: I: Patients Premedicated with Morphine Sulphate

The study was performed to determine the ED₅₀ and ED₉₅ of acontinuous infusion of the emulsion formulation of propofolduring 67% nitrous oxide anaestheisa in 57 patients premed-icatedwith morphine sulphate 0.15 mg kg^–1. Anaesthesia was inducedwith propofol 2 mg kg^–1, and maintained before incisionwith a fixed-rate infusion of propofol to supplement nitrousoxide. The response to the first surgical incision, made atleast 30 min after induction of anaesthesia, was observed. TheED₅₀; was 53.5 µg kg^–1 min^–1 and the ED₉₅was 112.2 µg kg^–1 min^–1. At the time of thefirst surgical incision, the venous whole blood concentrationsof propofol at the ED₅₀ and ED₉₅ infusion rates (EC₅₀and EC₉₅were 1.66 µg ml^–1 and 3.39 fig ml^–1 respectively.The satisfactory maintenance of anaesthesia provided by nitrousoxide supplemented with propofol was associated with stabilityand rapid, uncomplicated recovery.     

Hyperventilation reverses the nitrous oxide-induced increase cerebral blood flow velocity in human volunteers

Because hypocapnia is routine during general anaesthesia forintracranial procedures, we have compared, in 1 3 healthy volunteers,the effect of normocapnia (PE'_CO2 5.3 kPa) and hypocapnia (PE'_CO23.3 kPa) on mean blood flow velocity in the middle cerebralartery (Vmca) during normoventilation and hyperventilation withair and with 50% nitrous oxide in oxygen. After replacementof air with 50% nitrous oxide in oxygen, there was an increasein mean Vmca during normoventilation (air: mean 68.23 (SD 16.98)cm s^–1 vs nitrous oxide in oxygen: 90.69 (20.41) cm s^–1;P < 0.01), whereas during hyperventilation mean Vmca valueswere similar regardless of the inhaled gas mixture (air: 43.46(9.97) cm s^–1 vs nitrous oxide in oxygen: 41.69 (8.08)cm s^–1 Our data suggest that the nitrous oxide-inducedincrease in mean Vmca can be blocked by hyperventilation. (Br.J. Anaesth. 1995; 74: 616–618)     

Effects of sevoflurane and propofol on left ventricular diastolic function in patients with pre-existing diastolic dysfunction

Background. The effects of anaesthetics on left ventricular(LV) diastolic function in patients with pre-existing diastolicdysfunction are not well known. We hypothesized that propofolbut not sevoflurane will worsen the pre-existing LV diastolicdysfunction. Methods. Of 24 randomized patients, 23 fulfilled the predefinedechocardiographic criterion for diastolic dysfunction. Theyreceived general anaesthesia with sevoflurane 1 MAC (n=12) orpropofol 4 µg ml^–1 (n=11). Echocardiographic examinationswere performed at baseline and in anaesthetized patients underspontaneous breathing and under positive pressure ventilation.Analysis focused on peak early diastolic velocity of the mitralannulus (E_a). Results. During spontaneous breathing, E_a was higher in thesevoflurane than in the propofol group [mean (95% CI) 7.0 (5.9–8.1)vs 5.5 (4.7–6.3) cm s^–1; P<0.05], reflectingan increase of E_a from baseline only in the sevoflurane group(P<0.01). Haemodynamic findings were similar in both groups,but the end-tidal carbon dioxide content was more elevated inthe propofol group (P<0.01). During positive pressure ventilation,E_a was similarly low in the sevoflurane and propofol groups[5.3 (4.2–6.3) and 4.4 (3.6–5.2) cm s^–1, respectively]. Conclusions. During spontaneous breathing, early diastolic functionimproved in the sevoflurane but not in the propofol group. However,during positive pressure ventilation and balanced anaesthesia,there was no evidence of different effects caused by the twoanaesthetics.     

Esmolol prevents movement and attenuates the BIS response to orotracheal intubation

Background. Beta-adrenergic agonists enhance behavioural andelectroencephalographic arousal reactions. We explored whetheradding esmolol, a short-acting ß₁-adrenoceptor antagonist,to propofol anaesthesia modified the bispectral index (BIS)during induction of anaesthesia and orotracheal intubation. Methods. Fifty patients were randomly allocated, in a double-blindfashion, to receive esmolol 1 mg kg^–1 followed by 250µg kg^–1 min^–1 or saline (control). Esmololor saline was started 6 min after a target-controlled infusion(TCI) of propofol (effect-site concentration 4 µg ml^–1).After loss of consciousness, and before administration of vecuronium0.1 mg kg^–1, a tourniquet was applied to one arm and inflatedto 150 mm Hg greater than systolic pressure. Eleven minutesafter the TCI began, the trachea was intubated; gross movementwithin the first min after orotracheal intubation was recorded.BIS was recorded at 10-s intervals. Mean arterial pressure (MAP)and heart rate were measured non-invasively every min. Results. There were no intergroup differences in BIS, heartrate or MAP before laryngoscopy. BIS increased significantlyafter orotracheal intubation (compared with the pre-laryngoscopyvalues) in the control group only, with a maximum increase of40 (SD 18)% vs 8 (11)% in the esmolol group (P<0.01). Maximumchanges in heart rate [45 (19)% vs 23 (14)%] and MAP [62 (24)%vs 45 (23)%] with orotracheal intubation were also significantlygreater in the control group than in the esmolol group. Morepatients in the control than in the esmolol group moved afterorotracheal intubation (23 vs 12, P<0.01). Conclusion. Esmolol not only attenuated haemodynamic and somaticresponses to laryngoscopy and orotracheal intubation, but alsoprevented BIS arousal reactions in patients anaesthetized withpropofol. Br J Anaesth 2002; 89: 857–62     

Effects of phenylephrine and prostaglandin E on ventriculo-arterial matching during halothane anaesthesia

We have investigated the effects of phenylephrine alone andcombined with prostaglandin E₁ (PGE₁) on ventriculo-arterialmatching during halothane anaesthesia in dogs. The ratio ofleft ventricular end-systolic elastance (Ees) to effective arterialelastance (Ea) was used as an index of ventriculo-arterial matching.In group 1 (n = 7), measurements were performed at control,1.5% halothane, halothane+phenylephrine 1–10 µgkg^–1 min^–1, and halothane + phenylephrine + PGE₁,0.2–1.0 or 1.0–2.0 µg kg^–1 min^–1.In group 2 (n = 5), dobutamine 2 and 5 µg kg^–1 min^–1was infused during halothane anaesthesia. Halothane 1.5% decreasedmean arterial pressure (MAP), cardiac output and Ees. Phenylephrinerestored MAP, but further decreased cardiac output. The decreasein Ees produced by halothane was reversed by phenylephrine.PGE₁ increased cardiac output and reversed the increases inEa and Ea/Ees during phenylephrine infusion. Dobutamine alsoreversed halothane-induced decreases in MAP, cardiac outputand Ees, and improved Ea/Ees. Our results indicate that combineduse of PGE₁ with phenylephrine can eliminate the vasoconstrictiveproperty of phenylephrine, resulting in an improvement in ventriculo-arterialmatching.     

Effects of xenon anaesthesia on the circulatory response to hypoventilation

Background. Circulatory response to hypoventilation is aimedat eliminating carbon dioxide and maintaining oxygen delivery(DO₂) by increasing cardiac output (CO). The hypothesis thatthis increase is more pronounced with xenon than with isofluraneanaesthesia was tested in pigs. Methods. Twenty pigs received anaesthesia with xenon 0.55 MAC/remifentanil0.5 µg kg^–1 min^–1 (group X, n=10) or isoflurane0.55 MAC/remifentanil 0.5 µg kg^–1min^–1 (groupI, n=10). CO, heart rate (HR), mean arterial pressure (MAP)and left ventricular fractional area change (FAC) were measuredat baseline, after 5 and 15 min of hypoventilation and after5, 15 and 30 min of restored ventilation. Results. CO increased by 10–20% with both anaesthetics,with an equivalent rise in HR, maintaining DO₂ in spite of a20% reduction in arterial oxygen content. Decreased left ventricular(LV) afterload during hypoventilation increased FAC, and thiswas more marked with xenon (0.60–0.66, P<0.05 comparedwith baseline and isoflurane). This difference is attributedto negative inotropic effects of isoflurane. Increased pulmonaryvascular resistance during hypoventilation was found with bothanaesthetics. Conclusion. The cardiovascular effects observed in this modelof moderate hypoventilation were sufficient to maintain DO₂.Although the haemodynamic response appeared more pronouncedwith xenon, differences were not clinically relevant. An increasein FAC with xenon is attributed to its lack of negative inotropiceffects.     

Sevoflurane and propofol decrease intraocular pressure equally during non-ophthalmic surgery and recovery

Background. To provide good control of intraocular pressure(IOP) during anaesthesia and surgery, we conducted a study comparingthe effects on IOP during maintenance and recovery of sevofluranevs propofol anaesthesia in 33 patients (ASA I–II) undergoingelective non- ophthalmic surgery. Methods. Anaesthesia was induced with propofol 2 mg kg^–1,fentanyl 2 µg kg^–1 and vecuronium 0.1 mg kg^–1.Patients were allocated randomly to receive either propofol4–8 mg kg^–1 h^–1 (group P; n=16)or 1.5–2.5 vol% sevoflurane (group S; n=17) for maintenanceof anaesthesia. Fentanyl 2–4 µg kg^–1was added if necessary. The lungs were ventilated with 50% airin oxygen. Blood pressure, heart rate, oxygen saturation andend-tidal carbon dioxide were measured before and throughoutanaesthesia and in the recovery room. IOP was determined withapplanation tonometry (Perkins) by one ophthalmologist blindedto the anaesthetic technique. Results. There was a significant decrease in IOP after inductionand during maintenance of anaesthesia in both groups. No significantdifferences in IOP between the two groups was found. Conclusion. Sevoflurane maintains the IOP at an equally reducedlevel compared with propofol. Br J Anaesth 2002; 89: 764–6     

Midazolam versus propofol for reducing contractility of fatigued canine diaphragm

The effects of midazolam and propofol on the contractility offatigued canine diaphragm were examined. Diaphragmatic fatiguewas induced by intermittent supramaximal bilateral electrophrenicstimulation at a frequency of 20 Hz applied for 30 min.After fatigue had been induced, group I (n=10) receivedno study drug, group II (n=10) was given a propofol infusion(0.1 mg kg^–1 loading dose plus 1.5 mg kg^–1 h^–1maintenance dose) and group III (n=10) was given a midazolaminfusion (0.1 mg kg^–1 loading dose plus 0.1 mg kg^–1 h^–1maintenance dose). Diaphragmatic contractility was assessedby measuring transdiaphragmatic pressure (P_di). After the fatigue-inducingperiod in each group, P_di at low-frequency (20 Hz) stimulationwas lower than the baseline values (P<0.05), whereas no changein P_di at high-frequency (100 Hz) stimulation was observed.In group II, P_di at 20 Hz stimulation was lower than fatiguedvalues (P<0.05); P_di at 100 Hz stimulation did not change.In group III, P_di at both stimulation frequencies was lowerthan fatigued values (P<0.05). Compared with group I, P_diat 20 Hz stimulation was lower than fatigued values (P<0.05)during administration of the study drug in groups II and III.The decrease in P_di was greater in group III than in group II(P<0.05). In conclusion, midazolam compared with propofolis associated with an inhibitory effect on contractility inthe fatigued canine diaphragm. Br J Anaesth 2001; 86: 879–81     

EEG AND MEMORY EFFECTS OF LOW-DOSE INFUSIONS OF PROPOFOL

The purpose of this study was to identify EEG changes associatedwith low-dose propofol infusion producing only sedative effects,and to describe the memory effects of low-dose propofol infusion.Ten healthy volunteers underwent EEG monitoring (at F_z, C_z,P_z and O_z electrode sites) before, during and after propofol0.5mg kg^–1 i.v. bolus and 75 fig kg^–1 min^–1as an infusion. Mean serum concentration of propofol duringinfusion was 0.86 (SD 0.14) µg ml^–1. The EEG changedsignificantly during infusion, with increased power in the beta,(15–20 Hz). beta₂ (20.5–30 Hz) and delta (1–3.5Hz) frequencies. Beta₁ and beta₂ power changes were most markedat the F_z and C_z electrodes. Subjects were sedated, but ableto complete cognitive tasks. Visual analogue scales of attentionand sleepiness were obtained throughout the study and demonstrateda sedative effect during propofol infusion, but were not a significantfactor in memory performance or EEG changes. A verbal learningtask (Rey Auditory-Verbal Learning Task) administered before,during and after infusion showed a marked reduction in short-termmemory capacity and dramatically impaired free recall and recognitionduring infusion. Nine of 10 subjects had partial amnesia forcomplex visual scenes presented during infusion, recalling lessthan 50% of the material. Stronger cueing was required to retrieveinformation presented during propofol infusion, with an increasein mean retrieval time from 95.4 (41.2) s to 426.8 (83.1) s.EEG and memory effects resolved quickly after the end of infusion.We conclude that anterior, high frequency EEG activity increasessignificantly during low-dose propofol infusion and that propofolproduces significant memory impairment which has characteristicsof true amnesia, concurrent with changes in beta, power in theEEG. The fact that low-dose propofol produces significant changesin both cognitive and EEG measures warrants further investigationinto the utility of the EEG power spectrum as a useful monitorof amnesia during conscious sedation with propofol.      

EFFECTS OF ALFENTANIL ON CEREBRAL VASCULAR REACTIVITY IN DOGS

The effects of high dose alfentanil on the cerebral vascularresponses to alterations in mean arterial pressure (MAP), arterialoxygen tension (Pa^O2) and arterial carbon dioxide tension (Pa^CO2)were studied in 17 dogs, using the cerebral venous outflow technique.In six animals anaesthetized with sodium pentobarbitone 30 mgkg^–1 i.v., bolus injection of alfentanil 0.32 mg kg^–li.v. decreased MAP without a change in cerebral blood flow (CBF).In another group of animals(n = 5) anaesthetized with pentobarbitone30mg kg^–1 i.v. the CBF responses to changes in MAP. Pa^O2,and Pa^CO2 were studied. In a third group of animals (n = 6)anaesthetized with alfentanil 0.32 mg kg^–1 i.v. plus pentobarbitone1–2 mg kg^–1 i.v. and an infusion of alfentanil 0.32mg kg^–1h^–1 the CBF responses to alterations inMAP, Pa^O2, and Pa^CO2 were studied and compared with the barbiturate-anaesthetizedanimals. The CBF responses to hypercapnia and hypoxia in thealfentanil-anaesthetized animals were not different from thoseobserved in animals anaesthetized with barbiturate only. Thelower and upper limits of cerebral autoregulation in alfentanil-anaesthetizedanimals were not different from those observed in animals anaesthetizedwith barbiturate only. The data suggest that alfentanil, indoses sufficient to cause profound analgesia and anaesthesia,does not alter cerebral reactivity to changes in Pa^O2, Pa^CO2and MAP.     

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).     

IMPROVEMENT OF BRAIN ELECTRICAL ACTIVITY DURING TREATMENT OF PORCINE MALIGNANT HYPERTHERMIA WITH DANTROLENE

Three months before this study, susceptibility for malignanthyperthermia (MH) had been tested in 15 pigs. In all pigs, MHwas triggered by administration of 1% halothane. Brain electricalactivity was examined during therapy of MH with and withoutadministration of dantrolene. From the EEG, power densitiesin selected frequencies and the median frequency of the powerspectrum were calculated. Therapy was started when severe respiratorychanges were observed (Pa_co2 > 10 kPa, mixed venous oxygentension ( < 4 kPa. At this time, heart rate exceeded 150 beat min^–1, mean arterialpressure (MAP) was less than 60 mm Hg and median frequency wasless than 2 Hz. EEG was isoelectric (n=6) or showed slow polymorphicdelta-activity. For therapy, administration of all anaestheticswas terminated, 100% oxygen was delivered and ventilation wasincreased four-fold. Acidosis was treated by administrationof sodium bicarbonate 2–4 mmol litre^–1 kg^–1.Animals were allocated randomly to one of two groups: groupI (control, n=7) received no dantrolene; group II (n=8) receiveddantrolene 2.5 mg kg^–1 i.v. All variables were measuredover a period of 60 min after therapy: EEG, HR and MAP wererecorded continuously and blood-gas tensions, arterial po tassiumand glucose concentrations and pH were measured every 150 s.In group I (no dantrolene) minor, transient improvements inEEG activity were noted, but all animals died within 15–25mm after the start of therapy. In dantrolene-treated animals,EEG total power and median frequency increased within 5 min.The improvement in brain electrical activity occurred beforeany significant increases in MAP, Pa_o2 and or decreases in all Pa_co2 or potassium plasma concentration.Our results in dicate that dantrolene given for the treatmentof a fulminant MH crisis helps to improve, not only haemodynamicstate and metabolism, but also recovery of neuronal activity.(Br. J. Anaesth. 1993; 71: 881–884)     

Effects of short-term simultaneous infusion of dobutamine and terlipressin in patients with septic shock: the DOBUPRESS study

Background: Terlipressin bolus infusion may reduce cardiac output and globaloxygen supply. The present study was designed to determine whetherdobutamine may counterbalance the terlipressin-induced depressionin mixed-venous oxygen saturation (Sv_O2) in patients with catecholamine-dependentseptic shock. Methods: Prospective, randomized, controlled study performed in a universityhospital intensive care unit. Septic shock patients requiringa continuous infusion of norepinephrine (0.9 µg kg^–1min^–1) to maintain mean arterial pressure (MAP) at 70(SD 5) mm Hg were randomly allocated to be treated either with(i) sole norepinephrine infusion (control, n=20), (ii) a singledose of terlipressin 1 mg (n=19), or (iii) a single dose ofterlipressin 1 mg followed by dobutamine infusion titrated toreverse the anticipated reduction in Sv_O2 (n=20). Systemic,pulmonary, and regional haemodynamic variables were obtainedat baseline and after 2 and 4 h. Laboratory surrogate markersof organ (dys)function were tested at baseline and after 12and 24 h. Results: Terlipressin (with and without dobutamine) infusion preservedMAP at 70 (5) mm Hg, while allowing to reduce norepinephrinerequirements to 0.17 (0.2) and 0.2 (0.2) µg kg^–1min^–1, respectively [vs1.4 (0.3) µg kg^–1 min^–1in controls at 4 h; each P<0.001]. The terlipressin-linkeddecrease in Sv_O2 was reversed by dobutamine at a mean dose of20 (8) µg kg^–1 min^–1 [Sv_O2 at 4 h: 59 (11)%vs 69 (12)%, P=0.028]. Conclusions: In human catecholamine-dependent septic shock, terlipressin(with and without concomitant dobutamine infusion) increasesMAP and markedly reduces norepinephrine requirements. Althoughno adverse events were noticed in the present study, potentialbenefits of increasing Sv_O2 after terlipressin bolus infusionneed to be weighted against the risk of cardiovascular complicationsresulting from high-dose dobutamine.     

Beta2 adrenergic antagonist inhibits cerebral cortical oxygen delivery after severe haemodilution in rats

Background. Haemodilution has been associated with neurologicalmorbidity in surgical patients. This study tests the hypothesisthat inhibition of cerebral vasodilatation by systemic ß₂adrenergic blockade would impair cerebral oxygen delivery leadingto tissue hypoxia in severely haemodiluted rats. Methods. Under general anaesthesia, cerebral tissue probes wereplaced to measure temperature, regional cerebral blood flow(rCBF) and tissue oxygen tension (P_BrO₂) in the parietal cerebralcortex or hippocampus. Baseline measurements were establishedbefore and after systemic administration of either a ß₂antagonist (10 mg kg^–1 i.v., ICI 118, 551) or saline vehicle.Acute haemodilution was then performed by simultaneously exchanging50% of the estimated blood volume (30 ml kg^–1) with pentastarch.Arterial blood gases (ABGs), haemoglobin concentration (co-oximetry),mean arterial blood pressure (MAP) and heart rate (HR) werealso measured. Data were analysed using a two-way ANOVA andpost hoc Tukey's test [mean (SD)]. Results. Haemodilution reduced the haemoglobin concentrationcomparably in all groups [71 (9) g litre^–1]. There wereno differences in ABGs, co-oximetry, HR and MAP measurementsbetween control and ß₂ blocked rats, either beforeor 60 min after drug or vehicle administration. In rats treatedwith the ß₂ antagonist there was a significant reductionin parietal cerebral cortical temperature, regional blood flowand tissue oxygen tension, relative to control rats, 60 minafter haemodilution (P<0.05 for each). These differenceswere not observed when probes were placed in the hippocampus. Conclusion. Systemic ß₂ adrenergic blockade inhibitedthe compensatory increase in parietal cerebral cortical oxygendelivery after haemodilution thereby reducing cerebral corticaltissue oxygen tension.     

TOTAL I.V. ANAESTHESIA WITH PROPOFOL AND ALFENTANIL: DOSE REQUIREMENTS FOR PROPOFOL AND THE EFFECT OF PREMEDICATION WITH CLONIDINE

We determined in 51 healthy patients undergoing body surfacesurgery the dose requirements for propofol, as part of a totali.v. anaesthesia technique with an alfentanil infusion. Afterpremedication with temazepam, patients received alfentanil 50µg kg^–1 followed by an infusion of 50 µg kg^–1h^–1. Patients were anaesthetized with a loading dose ofpropofol followed by a three-stage infusion designed to reachone of five preselected blood concentrations of propofol. Themotor response to the initial surgical incision was noted andprobit analysis was used to derive the ED₅₀ (2.94 mg kg^–1h^–1; 95% confidence limits: 2.35–3.37 mg kg^–1h^–1). and ED₉₅ (4.98 mg kg^–1 h^–1; 95% limits:4.13–8.8 mg kg^–1 h^–1) for the final propololinfusion rate under these conditions. Whole blood concentrationof propofol at the time of the incision was related linearlyto the infusion rate and the EC₅₀ and EC₉₅ (probit analysis)were derived as 1.44 (95% confidence limits 0.62–1.87)and 4.05 (95% confidence limits 2.78–30.5) µg ml^–1,respectively. Postoperative recovery was rapid, uncomplicatedand uneventful. In a subgroup of eight patients, the additionof clonidine 0.6mg to the premedication significantly decreasedthe requirement for propofol (P <0.05) during surgery, butresulted in prolonged recovery times. Pilot study presented to the Anaesthetic Research Society, June24, 1988 [1].