Ringer's solution but not hydroxyethyl starch or modified fluid gelatin enhances platelet microvesicle formation in a porcine model of septic shock

Background. Sepsis is associated with volume deficit and clottingsystem activation. Platelet activation in sepsis results inan increased formation of microvesicles, which in turn, havebeen associated with increased mortality. We hypothesized aneffect of different volume replacement solutions on platelet-derivedmicrovesicle formation in septic shock. Methods. Anaesthetized, mechanically ventilated and multi-catheterizedpigs received 1 g kg^–1 body weight faeces into the abdominalcavity to induce sepsis and were observed over 8 h. Five animalsin each group received volume replacement therapy with modifiedfluid gelatin 4% or 8% (MFG4%, MFG8%), 6% hydroxyethylstarch(HES) 200/0.5 or Ringer’s solution (RS) to maintain acentral venous pressure of 12 mm Hg. Flow cytometry was usedfor determination of microvesicles before induction of sepsis(baseline) and after 8 h. Platelets and microvesicles were identifiedwith an anti-platelet monoclonal Ab and a secondary antibody.Microvesicles were determined as the smallest 1–3% positivecells in forward scatter. Intergroup comparisons were performedusing Wilks–Lambda and Ryan–Einot–Gabriel–WelshF-test. Differences within groups were compared using a two-tailedStudent’s t-test. Results. Baseline values were considered as 100%. While microvesicleformation was reduced in HES (73 (SD 19)%), MFG4% (63 (41)%)and MFG8% groups (53 (17)%), an increase in the RS-group (210(121)%) was observed. Eight hours after induction of sepsis,formation of microvesicles was significantly higher in the RSgroup compared to all colloid-treated groups. Conclusion. In this porcine septic shock model the formationof platelet-derived microvesicles was significantly increasedby volume replacement with Ringer’s solution in comparisonto colloid solutions. Br J Anaesth 2004; 92: 716–21     

Dobutamine compensates deleterious hemodynamic and metabolic effects of vasopressin in the splanchnic region in endotoxin shock

BACKGROUND: Vasopressin is a potent vasopressor in septic shock, but it may impair splanchnic perfusion. We compared the effects of vasopressin alone and in combination with dobutamine on systemic and splanchnic circulation and metabolism in porcine endotoxin shock. METHODS: Twelve pigs were randomized to receive either vasopressin (VASO, n = 6) or vasopressin in combination with dobutamine (DOBU, n = 6) during endotoxin shock (E. coli endotoxin infusion). Endotoxin infusion rate was increased to induce hypotension after which vasoactive drugs were started. We aimed to keep systemic mean arterial pressure (MAP) >70 mmHg by vasopressin; the goal of dobutamine infusion was to prevent decrease in cardiac output often associated with vasopressin infusion. Regional blood flows, oxygen delivery and consumption, arterial and regional lactate concentrations were measured. RESULTS: Mean arterial pressure >70 mmHg was achieved in both the VASO and DOBU groups. After the primary decrease of cardiac output by vasopressin, systemic blood flow remained stable in vasopressin-treated animals. However, vasopressin as a monotherapy decreased portal venous blood flow. This was prevented by dobutamine. Vasopressin also induced splanchnic lactate release and arterial hyperlactatemia, which were not observed when dobutamine was combined with vasopressin. CONCLUSION: Dobutamine prevents adverse hemodynamic and metabolic effects of vasopressin in septic shock.     

Beneficial effects of hypertonic saline/dextran on early survival in porcine endotoxin shock

BACKGROUND: Hypertonic saline/dextran (HSD) has been shown to have beneficial effects in haemorrhagic shock. These effects, with improved haemodynamics and organ perfusion, would in theory also be of benefit in septic shock. However, this is less studied. We have therefore further evaluated the effect of additional treatment with HSD in a porcine endotoxin shock model. METHODS: Sixteen anaesthetized pigs were used. A continuous infusion of endotoxin (LPS EC) was increased stepwise during 30 min to a rate of 5 microg/kg/h. The infusion was discontinued after 3 h and the animals were observed for another 2 h. The animals received continuous basal fluid resuscitation with isotonic Ringer's glucose 2.5% at a rate of 20 ml/kg/h throughout the experiment. After 1 h of endotoxin infusion, the animals were randomized to additional treatment with HSD, 4 ml/kg over 5 min, or the same volume of isotonic saline. Every 30 min, haemodynamics and mixed venous saturation (SvO2) were measured via a pulmonary artery catheter. Regional blood flow rates were measured continuously by perivascular ultrasonic flow probes. The metabolic response was measured by arterial blood gas analysis. RESULTS: The endotoxin put all animals into a progressive hypodynamic circulatory shock during the experiment. Treatment with HSD improved survival rate to 8/8 compared with controls 3/8. There was a transient circulatory recovery with improved central and regional haemodynamics, accompanied by stabilized metabolic response. CONCLUSION: Treatment with additional HSD improves survival in an early phase of endotoxin shock. Generally improved haemodynamics and oxygenation of peripheral tissues are suggested as possible mechanisms.     

Cerebral haemodynamics in pregnancy and pre-eclampsia as assessed by transcranial Doppler ultrasonography

Background. Altered cerebral circulation, as reported duringnormal pregnancy, and in patients with pre-eclampsia, can beassociated with changes in cerebral vascular reactivity and/orcerebral autoregulation. The aim of our study was to performa comparative assessment of cerebral haemodynamics, includingvascular reactivity and autoregulation, in pre-eclamptic patients,healthy pregnant women, and healthy non-pregnant women. Methods. Thirty patients with pre-eclampsia were recruited.Age- and height-matched healthy pregnant (n=30) and non-pregnantcontrol (n=30) groups were also recruited. Monitoring includedtranscranial Doppler ultrasonography, end-tidal carbon dioxideand non-invasive arterial pressure measurement. Cerebral autoregulationwas assessed by performing the transient hyperaemic response(THR) test. The cerebrovascular reactivity to carbon dioxide(CRCO₂) was assessed by measuring middle cerebral artery bloodflow velocity (MCAFV) after induced changes in end-tidal carbondioxide. Estimated cerebral perfusion pressure (eCPP) and criticalclosing pressure (CrCP) were calculated using established formulae.Statistical analysis included ANOVA with Tukey’s pairwisecomparisons. Results. Mean arterial pressure (MAP) was increased in pre-eclampsia(P<0.05). Mean MCAFV was lower in healthy pregnancy (P<0.05),but in pre-eclampsia it was similar to the non- pregnant group.When compared with the non-pregnant group, mean eCPP was higherin the healthy pregnant and pre-eclamptic groups (P<0.05).There were no meaningful differences in cerebral autoregulationor CRCO₂. Conclusions. Healthy pregnancy increases eCPP, presumably bydecreasing CrCP. In pre-eclampsia, eCPP is maintained at thesame level as in healthy pregnancy despite an increased MAP.Pre-eclampsia has no significant effect on cerebral autoregulationor CRCO₂. Br J Anaesth 2002; 89: 687–92     

Comparison of lactated Ringer's, gelatine and blood resuscitation on intestinal oxygen supply and mucosal tissue oxygen tension in haemorrhagic shock

Objectives. To evaluate the effects on intestinal oxygen supply,and mucosal tissue oxygen tension during haemorrhage and afterfluid resuscitation with either blood (B; n=7), gelatine (G;n=8), or lactated Ringer's solution (R; n=8) in an autoperfused,innervated jejunal segment in anaesthetized pigs. Methods. To induce haemorrhagic shock, 50% of calculated bloodvolume was withdrawn. Systemic haemodynamics, mesenteric venousand systemic acid–base and blood gas variables, and lactatemeasurements were recorded. A flowmeter was used for measuringmesenteric arterial blood flow. Mucosal tissue oxygen tension(PO₂muc), jejunal microvascular haemoglobin oxygen saturation(HbO₂) and microvascular blood flow were measured. Measurementswere performed at baseline, after haemorrhage and at four 20min intervals after fluid resuscitation. After haemorrhage,animals were retransfused with blood, gelatine or lactated Ringer'ssolution until baseline pulmonary capillary wedge pressure wasreached. Results. After resuscitation, no significant differences inmacrohaemodynamic parameters were observed between groups. Systemicand intestinal lactate concentration was significantly increasedin animals receiving lactated Ringer's solution [5.6 (1.1) vs3.3 (1.1) mmol litre^–1; 5.6 (1.1) vs 3.3 (1.2) mmol litre^–1].Oxygen supply to the intestine was impaired in animals receivinglactated Ringer's solution when compared with animals receivingblood. Blood and gelatine resuscitation resulted in higher HbO₂than with lactated Ringer's resuscitation after haemorrhagicshock [B, 43.8 (10.4)%; G, 34.6 (9.4)%; R, 28.0 (9.3)%]. PO₂mucwas better preserved with gelatine resuscitation when comparedwith lactated Ringer's or blood resuscitation [20.0 (8.8) vs13.8 (7.1) mm Hg, 15.2 (7.2) mm Hg, respectively]. Conclusion. Blood or gelatine infusion improves mucosal tissueoxygenation of the porcine jejunum after severe haemorrhagewhen compared with lactated Ringer's solution.     

Effects of AM281, a cannabinoid antagonist, on circulatory deterioration and cytokine production in an endotoxin shock model: comparison with norepinephrine

Purpose The purpose of this study was to examine the comparative effects of AM281, a cannabinoid antagonist, and norepinephrine (NE) on systemic hemodynamics, and renal and mesenteric artery blood flow in an endotoxin shock model. Methods The study was designed to include two sets of experiments: (1) measurements of changes in systemic hemodynamics and organ artery blood flows (n = 20), and (2) measurements of biochemical variables (n = 20). For each set of experiments, male 7-week-old Wistar rats were randomly divided into four groups: group 1, controls (n = 5); group 2, receiving lipopolysaccharide (LPS: Escherichia coli endotoxin, 10.0 mg·kg⁻¹ intravenous bolus) (n = 5); group 3, receiving intravenous LPS and NE (continuous infusion at 0.2 μg·kg·min⁻¹) (n = 5); group 4, receiving LPS and AM281 (0.1 mg·kg·min⁻¹) (n = 5). Systemic hemodynamics, regional artery blood flow changes, and biochemical variables were assessed before treatment and 1 and 3 h after treatment. Results Infusion of NE or AM281 prevented endotoxin-induced decreases in systemic arterial pressure, aortic blood flow, carotid artery blood flow, and renal artery blood flow. Both AM281 and NE inhibited endotoxin-induced increases in cytokine production, with significant differences observed among the three groups at 1 and 3 h after treatment. Endotoxin-induced decreases in mesenteric arterial blood flow were restored by AM281 but not by NE. AM281 improved arterial oxygenation and reduced lactate overproduction and body temperature elevation induced by endotoxin. Conclusions Although NE and AM281 both prevented endotoxin-induced deterioration of systemic hemodynamics, AM281 yielded better preservation of mesenteric blood flow and attenuation of cytokine production than NE.     

Correlating in vivo anaesthetic effects with ex vivo receptor density data supports a GABAergic mechanism of action for propofol, but not for isoflurane

If the in vivo effects of anaesthesia are mediated through aspecific receptor system, then a relationship could exist betweenthe regional changes in brain metabolism caused by a particularagent and the underlying regional distribution of the specificreceptors affected by that agent. Positron emission tomographydata from volunteers studied while unconscious during propofol(n=8) or isoflurane (n=5) anaesthesia were used retrospectivelyto explore for evidence of relationships between regional anaestheticeffects on brain glucose metabolism and known (ex vivo) regionaldistribution patterns of human receptor binding sites. The regionalmetabolic reductions caused by propofol differed significantlyfrom those of isoflurane. Propofol’s reductions negativelycorrelated most significantly with the regional distributionof [³H]diazepam and [³H]flunitrazepam (benzodiazepine) bindingsite densities (r=–0.86, P<0.0005; r=–0.79, P<0.005,respectively) and less strongly with [³H]naloxone (opioid) bindingdensity (r=–0.69, P<0.05). Isoflurane’s reductionspositively correlated only with muscarinic (acetylcholine) bindingdensity (r=0.85, P<0.05). These findings are consistent withthe hypothesis that some of propofol’s in vivo anaestheticeffects may be mediated through a GABAergic mechanism and suggestsome of isoflurane’s in vivo effects might involve antagonismof central acetylcholine functioning. Br J Anaesth 2001; 86: 618–26     

Nitric oxide and liver microcirculation during autoregulation and haemorrhagic shock in rabbit model

Background. Direct evidence of nitric oxide (NO) involvementin the regulation of hepatic microcirculation is not yet availableunder physiological conditions nor in haemorrhagic shock. Methods. A laser Doppler flowmetry was used to measure liverperfusion index and a specific NO-sensitive electrode was insertedinto liver parenchyma of anaesthetized rabbits. Hepatic autoregulationduring moderate hypovolaemia {mean arterial pressure at 50 mmHg without liver perfusion alteration; blood withdrawal 17.7(4.2) ml [mean (SD)]} or haemorrhagic shock [mean arterial pressureat 20 mm Hg associated with liver perfusion impairment and lacticacidosis; blood withdrawal 56.0 (6.8) ml] were investigatedover 60 min and were followed by a rapid infusion of the shedblood. Involvement of NO synthases was evaluated using a non-specificinhibitor, NAPNA (N-nitro-L-arginine P-nitro-anilide). Results. In the autoregulation group, a decrease [30.0 (4.0)mm Hg] of mean arterial pressure did not alter liver perfusionindex, whereas the liver NO concentration increased and reacheda plateau [125 (10)%; compared with baseline; P<0.05]. ThisNO concentration was reduced to zero by the administration ofNO synthase inhibitor. Haemorrhagic shock led to a rapid decreasein liver perfusion index [60 (7)%; compared with baseline; P<0.05]before an immediate and continuous increase in NO concentration[250 (50)%; compared with baseline; P<0.05]. Infusion ofNO inhibitor before haemorrhagic shock reduced the NO concentrationto zero and hepatic perfusion by 60 (8)% (P<0.05) of thebaseline. Mean arterial pressure increased simultaneously. Inthese animals, during haemorrhage, a continuous increase inNO concentration still occurred and liver perfusion slightlyincreased. In all groups but NAPNA+haemorrhagic shock, bloodreplacement induced recovery of baseline values. Conclusions. NO plays a physiological role in the liver microcirculationduring autoregulation. Its production is enzyme-dependent. Conversely,haemorrhagic shock induces a rapid increase in hepatic NO thatis at least partially enzyme-independent.     

Comparative effects of propofol vs dexmedetomidine on cerebrovascular carbon dioxide reactivity in patients with septic shock

Background: The use of sedative drugs is reportedly related to altered cerebrovascularCO₂ reactivity. The present study examined the comparative effectsof propofol vs dexmedetomidine on cerebrovascular CO₂ reactivityin patients with septic shock. Methods: A total of 20 patients with septic shock who required mechanicalventilation were included in this study. Sedation during mechanicalventilation was maintained using either propofol or dexmedetomidine.A 2.5 MHz pulsed transcranial Doppler probe was attached tothe head of the patient at the right temporal window for continuousmeasurement of mean blood flow velocity in the middle cerebralartery (V_mca). After establishing baseline values of V_mca andcardiovascular haemodynamics, end-tidal CO₂ was increased bydecreasing ventilatory frequency by 5–8 bpm. Results: The absolute and relative CO₂ reactivity values in patientswith septic shock were lower for both propofol and dexmedetomidinethan those for control groups, with significant differencesbetween these values in the two septic shock groups (absoluteCO₂ reactivity in septic shock under propofol: 2.6 (SD 0.3)cm s^–1 mm Hg^–1; absolute CO₂ reactivity in septicshock under dexmedetomidine: 2.0 (0.3) cm s^–1 mm Hg^–1;P<0.01). Conclusions: This study showed that cerebrovascular CO₂ reactivity was lowerunder dexmedetomidine sedation than under propofol sedationduring almost identical sedation in patients with septic shock.     

Intestinal and hepatic perfusion and metabolism in hypodynamic endotoxic shock. Effects of nitric oxide synthase inhibition

Background: Inhibition of nitric oxide synthase (NOS) has been claimed to be beneficial in septic shock. We investigated the overall and regional effects of a NOS-inhibitor on perfusion and metabolism during severe endotoxic shock.
Methods: Nineteen anaesthetised pigs were catheterised and ultrasonic flow-probes were placed around the portal vein, the hepatic artery, and the superior mesenteric artery. Thirteen animals were given a 3-h infusion of endotoxin; in 6 of these an infusion of N^G-nitro-L-arginine-methyl-ester (L-NAME) was started an hour after the start of endotoxin while 7 animals served as controls and received endotoxin only. Six animals were sham operated with no further intervention.
Results: Endotoxin produced a hypodynamic shock with pulmonary hypertension. L-NAME did not increase arterial blood pressure, but deepened the fall in cardiac output and enhanced the increase in systemic and pulmonary vascular resistance. The infusion of endotoxin caused a decrease in flows in all regions. The addition of L-NAME induced a further decrease in the mesenteric artery flow only. L-NAME had no additional effect on hepatic artery flow ratio, while a transient decrease was seen in mesenteric flow ratio. Portal flow ratio decreased in the control group only. Global as well as regional oxygen extraction increased in both groups, more so in the L-NAME group. Lactate levels increased with no differences between the groups.
Conclusion: In hypodynamic endotoxic shock, L-NAME infusion enhanced pulmonary vasoconstriction and increased left ventricular afterload. The resulting hypoperfusion caused an increase in mortality. The effects of L-NAME on global and mesenteric blood flow and metabolism were similar, while L-NAME had no additional effects on hepatic hypoperfusion or oxygen extraction. Thus, nitric oxide does not seem to be a major factor in the preservation of hepatic perfusion during unresuscitated endotoxic shock.     

Effects of sodium nitroprusside on splanchnic microcirculation in a resuscitated porcine model of septic shock

BACKGROUND: We tested the hypothesis that sodium nitroprusside (SNP) might improve the impairment of hepatosplanchnic microcirculatory blood flow (MBF) in septic shock. METHODS: Fourteen pigs were anaesthetized and their lungs mechanically ventilated. Sepsis was induced with i.v. infusion of live Pseudomonas aeruginosa [1x10(8) colony forming units (CFU) ml(-1) kg(-1)] for 1 h. Sixty minutes later, the animals received in a random succession either SNP or normal saline for 30 min. Mean arterial pressure (MAP), cardiac index (CI), mean pulmonary artery pressure (MPAP), carbon dioxide tension of the ileal mucosa (PCO2; by gas tonometry), ileal mucosal and hepatic MBF by laser Doppler flowmetry, blood gases, and lactates were assessed before, during administration, and 30 min after discontinuing the test drug. RESULTS: Bacterial infusion promoted hypodynamic shock (MAP -18%, CI -33%, ileal MBF -19%, and hepatic MBF -27%), which was converted to normodynamic shock by resuscitation. During SNP infusion, ileal mucosal MBF significantly increased (+19%) compared with control (P = 0.033). Although hepatic MBF increased (+42% from baseline), this did not differ from control. In order to maintain a constant central venous pressure and MAP, fluid loading and norepinephrine (P < 0.01) were increased. Acid-base status was not altered by SNP. CONCLUSIONS: In a resuscitated porcine model of the early phase of septic shock, SNP improved ileal mucosal MBF but required a concomitant increase in fluid and norepinephrine supplements to maintain constant systemic haemodynamic parameters.     

Lidocaine reduces ischaemic but not reperfusion injury in isolated rat heart

The local anaesthetic lidocaine protects the myocardium in ischaemia–reperfusionsituations. It is not known if this is the consequence of ananti-ischaemic effect or an effect on reperfusion injury. Therefore,we investigated the effect of two concentrations of lidocaineon myocardial ischaemia–reperfusion injury and on reperfusioninjury alone. We used an isolated rat heart model where heartrate, ventricular volume and coronary flow were kept constant.Hearts underwent 45 min of low-flow ischaemia followed by 90min reperfusion. Two groups received lidocaine 1.7 or 17 µgml^–1 starting 5 min before the onset of reperfusion. Intwo additional groups, lidocaine infusion started 5 min beforelow-flow ischaemia. In all groups, lidocaine administrationwas stopped after 15 min of reperfusion. One group served asan untreated control (n=11 in each group). Left ventriculardeveloped pressure (LVDP) and total creatine kinase release(CKR) were measured. Lidocaine administration during ischaemiaand reperfusion led to an improved recovery of LVDP during reperfusion(1.7 µg ml^–1, 54 (SEM 10) mm Hg; 17 µg ml^–1,71 (9) mm Hg at 30 min of reperfusion; both significantly differentfrom control (21 (4) mm Hg) (P<0.05)) and a reduced CKR (1.7µg ml^–1, 79 (13) IU; 17 µg ml^–1, 52(8) IU at 30 min of reperfusion; both significantly differentfrom control (130 (8) IU (P<0.05)). Lidocaine given duringearly reperfusion only, affected neither LVDP during reperfusion(1.7 µg ml^–1, 19 (6) mm Hg (P=1.0); 17 µgml^–1, 36 (8) mm Hg (P=0.46)) nor CKR (156 (21) IU (P=0.50)and 106 (14) IU (P=0.57)). We conclude that lidocaine protectsthe myocardium against ischaemic but not against reperfusioninjury in the isolated rat heart. Br J Anaesth 2001; 86: 846–52     

Does the optimization of cardiac output by fluid loading increase splanchnic blood flow?

We studied the effects of increasing cardiac output by fluidloading on splanchnic blood flow in patients with haemodynamicallystabilized septic shock. Eight patients (five female, 39–86yr) were assessed using a transpulmonary thermo-dye-dilutiontechnique for the measurement of cardiac index (CI) intrathoracicblood volume (ITBV) as a marker of cardiac preload and totalblood volume (TBV). Splanchnic blood flow was measured by thesteady state indocyanine-green technique using a hepatic venouscatheter. Gastric mucosal blood flow was estimated by regionalcarbon dioxide tension (PR_CO2). Hydroxyethyl starch was infusedto increase cardiac output while mean arterial pressure waskept constant. In parallel, mean norepinephrine dosage couldbe reduced from 0.59 to 0.33 µg kg^–1 min^–1.Mean (SD) TBV index increased from 2549 (365) to 3125 (447)ml m^–2, as did ITBV index from 888 (167) to 1075 (266)ml m^–2 and CI from 3.6 (1.0) to 4.6 (1.0) litre min^–1m^–2. Despite marked individual differences, splanchnicblood flow did not change significantly neither absolutely (from1.09 (0.96) to 1.19 (0.91) litre min^–1 m^–2) norfractionally as part of CI (from 28.4 (19.5) to 24.9 (16.3)%).Gastric mucosal PR_CO2 increased from 7.7 (2.6) to 8.3 (3.1)kPa. The PCO₂-gap, the difference between regional and end-tidalPCO₂, increased slightly from 3.2 (2.7) to 3.4 (3.1) kPa. Thus,an increase in cardiac output as a result of fluid loading isnot necessarily associated with an increase in splanchnic bloodflow in patients with stabilized septic shock. Br J Anaesth 2001; 86: 657–62     

Effects of ephedrine, dobutamine and dopexamine on cerebral haemodynamics: transcranial Doppler studies in healthy volunteers

Background. Sympathomimetic drugs are assumed to have no directeffects on cerebral haemodynamics on the basis of animal experiments;there is little evidence of their direct effects in humans.This study aimed to address this issue. Methods. The effects of ephedrine, dobutamine, and dopexamineon cerebral autoregulation, cerebral vascular reactivity tocarbon dioxide, estimated cerebral perfusion pressure, and zeroflow pressure (ZPF) were studied in 10 healthy volunteers usingtranscranial Doppler ultrasound. The strength of autoregulationwas measured using the transient hyperaemic response test. Thereactivity to carbon dioxide was measured as the change in middlecerebral artery flow velocity with a step change in end-tidalcarbon dioxide. For the estimated cerebral perfusion pressureand the ZFP, established formulae were used which utilized instantaneousvalues of arterial pressure and middle cerebral artery flowvelocity. Measurements were made at baseline and after i.v.infusion of the study drug to an endpoint of 25% increase inmean arterial pressure (MAP) (ephedrine, dobutamine) or cardiacindex (dopexamine). Results. There was no significant change in the strength ofautoregulation (from (mean (SD)) 1.07 (0.16) to 1.07 (0.18);from 1.07 (0.16) to 1.03 (0.19); from 1.04 (0.12) to 1.04 (0.25)),reactivity to carbon dioxide (from 40% (8) to 36 (10); from37 (12) to 37 (11); from 45 (12) to 43 (11)) with ephedrine,dobutamine, or dopexamine, respectively. Despite a clinicallysignificant increase in MAP with ephedrine and dobutamine anda clinically significant increase in cardiac index with dopexamine,the estimated cerebral perfusion pressure did not change significantly(from 81 (38) to 60 (16) mm Hg with ephedrine; from 67 (22)to 63 (11) mm Hg with dobutamine; from 87 (27) to 79 (17) mmHg with dopexamine). The ZFP increased significantly with ephedrine(from 29 (10) to 44 (11) mm Hg) and dobutamine (from 35 (14)to 43 (10) mm Hg) but not dopexamine (from 3 (23) to 11 (22)mm Hg). Conclusions. Sympathomimetic agents do not significantly changecerebrovascular homeostasis as assessed by the transient hyperaemicresponse test, reactivity to carbon dioxide and estimated cerebralperfusion pressure. Br J Anaesth 2004; 92: 39–44     

Effects of AM281, a cannabinoid antagonist, on systemic haemodynamics, internal carotid artery blood flow and mortality in septic shock in rats

Introduction. The purpose of this study was to examine the effectsof AM281, a cannabinoid receptor antagonist, on systemic haemodynamics,internal carotid artery blood flow and mortality during septicshock in rats. Methods. The study included three sets of experiments: measurementsof changes in systemic haemodynamics and left internal carotidartery flow (30 animals divided into three groups of 10); measurementsof biochemical variables (n=30); assessment of mortality (n=30).Male Wistar rats (7 weeks old) were randomly divided into threegroups: group 1, control; group 2, lipopolysaccharide (LPS)i.v., Escherichia coli endotoxin 10.0 mg kg^–1 i.v., bolus;group 3, LPS 10.0 mg kg^–1 i.v.+AM281 1 mg kg^–1 i.v.Systemic haemodynamics, carotid artery flow changes and biochemicalvariables were assessed at pretreatment and 1, 2 and 3 h afterthe treatment was performed. Results. Administration of AM281 could prevent the haemodynamicchanges induced by sepsis. Tumour necrosis factor-     

Clinical evaluation of circulating blood volume in critically ill patients--contribution of a clinical scoring system

The circulating blood volume (CBV) of critically ill patientsmay be difficult to estimate on the basis of history and physicalexamination. The aim of this study was to evaluate the abilityof seven clinical signs and central venous pressure (CVP) topredict CBV in critically ill patients; CBV was evaluated withthe [¹²⁵I]human serum albumin technique. A scoring system wasconstructed using a combination of independence Bayes methodand logistic regression. Sixty-eight patients constituted a‘model development’ sample and 30 patients a validationsample. Thirty-six patients (53%) in the model development samplewere found to have a low CBV (measured CBV at least 10% lowerthan the predicted mean normal CBV). Neither the haemodynamicvariables monitored in ICU, nor the spot urinary sodium concentrationswere different between patients with and without a low CBV.Individually, none of the clinical signs tested have a goodpositive or negative predictive value. For CVP, only extremevalues seem to have clinical significance. To construct thescore, the signs tested were ranked according to their discriminatingefficacy. The probability of a low CBV was obtained by addingthe weights of each sign tested and converting the score obtainedinto a probability. On a validation sample of 30 patients, thepredictions are reliable as assessed by Z statistics rangingbetween –2 and +2. Our results suggest that: (1) individually,no clinical sign presented a clinical useful predictive value;and (2) a clinical scoring system may be helpful for the evaluationof CBV in critically ill patients. Br J Anaesth 2001; 86: 754–62     

Effect of diclofenac on cerebral blood flow velocity in patients with supratentorial tumours

Background. The aim of this investigation was to determine theeffects of diclofenac on cerebral blood flow. Middle cerebralartery blood flow velocity was measured in nine patients withsupratentorial tumours. Methods. Using a transcranial Doppler ultrasound, we measuredthe baseline mean and systolic cerebral blood flow velocity.Measurements were repeated following administration of diclofenac75 mg i.v. Results. There was no significant change in cerebral blood flowvelocity. All other physiological variables remained constant. Conclusion. Diclofenac does not cause a significant change incerebral blood flow velocity in patients with supratentorialtumours. Br J Anaesth 2002; 89: 762–4     

Effects of tracheal extubation on coronary blood flow,myocardial metabolism and systemic haemodynamic responses

Global coronary blood flow and metabolism were measured in seven patients on the first postoperative day following coronary revascularization to test the hypothesis that tracheal extubation produces adverse haemodynamic responses akin to those observed during tracheal intubation. Regional coronary flow and metabolic measurements were made in five of the seven patients. Extubation from a continuous positive airway pressure (CPAP) of 5 cm H₂O was associated with a statistically significant rise in cardiac index from 3.44 ± 0.23 L · min^-1 · m^-2 to 3.73 ± 0.15L·min^-1 ·m^-2 related to an increase in stroke index, without significant changes in heart rate, mean arterial and pulmonary capillary wedge pressure. Consequently the changes in myocardial oxygen consumption (8.52 ± 0.55 to 8.85 ± 0.93 ml · min^-1) and coronary blood flow (172 ± 18 to 179 ± 17 ml·min^-1) were less prominent than those reported during intubation, where substantial rises in myocardial oxygen consumption and coronary flow occurred. Two patients experienced cardiac lactate production but there were no changes in systemic or coronary haemodynamics, nor were there clinical or electrocardiographic signs of ischaemia. We conclude that extubation does not appear to be associated with adverse systemic or coronary haemodynamic responses in patients following coronary bypass grafting. However, the revascularized myocardium may remain vulnerable to anaerobic metabolism in the immediate postoperative period. Pour savoir si comme ľintubation, ľextubation de la trachée provoque des perturbations hémodynamiques, on a mesuré le métabolisme et la circulation coronarienne globale chez sept patients, au lendemain ďun pontage aorto-coronarien. On a aussi calculé les valeurs régionales de ces mêmes variables pour cinq ďentre eux. Ľindex cardiaque de 3.44 ± 0.23 L · min^-1 · m^-2 sous pression positive en respiration spontanée (CPAP) de 5 cm. H₂O s’est élevé à 3.73 ± 0.15 L · min^-1 · m^-2 post-extubation avec une augmentation significative du volume ďéjection. La fréquence cardiaque et les pressions artérielles moyennes et capillaires pulmonaires n’ont pas changé. Ainsi ľaugmentation de la consommation ďoxygène du myocarde de 8.52 ± 0.55 à 8.85 ± 0.93 ml · min^-1 et celle du flot coronarien de 172 ± 18 à 179 ± 17 ml · min^-1 ont été moindres que celles, importantes, déjà observées lors de ľintubation. On a noté chez deux patients une production de lactate par le myocarde, sans changement de ľhémodynamic systémique et coronarienne non plus que de signe clinique ou électrocardiographique ďischémie. Donc, après un pontage coronarien, ľextubation ne semble pas causer ďeffet néfaste sur les circulations systémique et coronarienne, toutefois, le myocarde revascularisé peut demeurer sensible au métabolisme anaérobique.     

Effects of haemoglobin-based oxygen carrier hemoglobin glutamer-200 (bovine) on intestinal perfusion and oxygenation in a canine hypovolaemia model

The objective of this investigation was to study the effectsof the first marketed haemoglobin-based oxygen carrier, Hemoglobinglutamer-200 (bovine) (Hb-200) (Oxyglobin^®) on splanchnicperfusion and oxygenation in a canine model of acute hypovolaemia.Twelve anaesthetized dogs [mean weight 30.8 (S.D. 1.4) kg] wereinstrumented for recordings of heart rate (HR), mean arterialpressure (MAP), central venous pressure (CVP), cardiac outputand cranial mesenteric arterial (CMA) and venous blood flows(CMV). Total and plasma haemoglobin (Hb), oxygen content andsaturation, lactate concentration, pH and blood gases were analysedin arterial, mixed venous and mesenteric venous blood samples.Measurements were made before (baseline) and after 1 hof haemorrhage, after which animals were resuscitated with eithershed blood (controls) or Hb-200 until HR, MAP and CVP returnedto prehaemorrhage levels. Recordings were repeated immediatelyand 3 h after termination of fluid resuscitation, afterwhich organ specimens were obtained for microscopic examination.Haemorrhage (average 32 ml kg^–1) reduced MAPto 50 mm Hg, increased HR and systemic vascular resistance(SVR), and was accompanied in both the systemic and the splanchniccirculation by significant decreases in blood flow, Hb contentand oxygen delivery (DO₂), and lactic acidosis. In controls,all variables recovered to baseline after isovolaemic resuscitationwith shed blood. In dogs resuscitated with a small volume ofHb-200 (10 ml kg^–1), HR, MAP, CVP and CMA andCMV blood flows returned to baseline. However, cardiac output,total Hb, oxygen content and systemic and mesenteric DO₂ remaineddepressed while SVR increased further. Mesenteric and systemicacid–base status recovered in both groups, and there wasno difference in microscopic tissue damage between groups. Thus,Hb-200 reconstituted splanchnic perfusion and oxidative metabolismin spite of pronounced systemic vasoconstriction and insufficientrestoration of CO and DO₂; it may improve diffusive oxygen transportin the microvasculature by virtue of haemodilution and its highefficiency in the uptake and release of oxygen. Br J Anaesth 2001; 86: 683–92     

Use of multi-plane transoesophageal echocardiography in visualization of the main hepatic veins and acquisition of Doppler sonography curves. Comparison with the transabdominal approach

The role of multi-plane transoesophageal echocardiography (TOE)in the visualization of the three main hepatic veins and acquisitionof Doppler sonography curves has not been established. We havestudied this diagnostic option of TOE in 34 patients duringgeneral anaesthesia. The findings were compared with the resultsof conventional transabdominal sonography (TAS). Using TOE,each of the three main hepatic veins could be visualized inall patients. In contrast, TAS allowed adequate two-dimensionalvisualization of the right, middle, and left hepatic vein inonly 97%, 85%, and 61% of the patients, respectively. AdequateDoppler tracings of the right and middle hepatic vein couldbe obtained in 100% and 97% of the patients by TOE and in 91%and 50% of the patients by TAS. Doppler tracings of the lefthepatic vein could only be acquired in 18% of the patients byTOE, but in 47% of the patients by TAS. As blood flow may becalculated from the diameter of the vessel, velocity time integralof the Doppler curve and heart rate, TOE may provide an interestingnon-invasive tool to monitor blood flow in the right and middlehepatic vein. Br J Anaesth 2001; 87: 711–7