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     

Lactic acidosis in the rectal lumen of patients with septic shock measured by luminal equilibrium dialysis

Background. Gut ischaemia may contribute to morbidity in sepsis,but little is known about the metabolic state of the gut mucosain such patients. Methods. Nine patients with abdominal septic shock treated withnorepinephrine, and ten healthy subjects, were subjected toequilibrium dialysis with a rectal balloon. pH, PCO₂ and concentrationsof L-lactate were measured by auto-analyser. Results. In rectal dialysis fluid from patients with septicshock, acidosis was present (pH 7.23, 95% CI 7.11–7.36)and concentrations of L-lactate were approximately five timesgreater than controls (2.5–5.8 vs 0.5–1.2 mmollitre^–1). The lactate concentration was related to thedose of norepinephrine (P<0.001). In contrast, values ofdialysate PCO₂ did not differ significantly between patientsand controls (6.4–11.0 vs 8.9–13.8 kPa). Conclusions. The results suggest that, either lactic acidosisin rectal mucosa is related to shock severity, or that norepinephrinecauses mucosal ischaemia. In any case, metabolic dysfunctionis present in the rectal mucosa in patients with abdominal septicshock treated with norepinephrine. Br J Anaesth 2002; 89: 919–22     

Genotype and interleukin-10 responses after cardiopulmonary bypass

Background. The pro- and anti-inflammatory cytokine balancehas been implicated in outcome from inflammatory conditions,and cardiopulmonary bypass is associated with a marked inflammatoryresponse. Interleukin-10 (IL-10) is an anti-inflammatory cytokineand levels have been shown to be highest in those patients whodevelop sepsis after trauma or surgery. IL-10 levels vary betweenindividuals and genotype may dictate the IL-10 response. Wetherefore investigated IL-10 genotype, circulating IL-10 concentrationsand outcome in terms of organ dysfunction 24 h after cardiopulmonarybypass. Methods. Blood samples were obtained from 150 patients before,and 3, and 24 h after cardiopulmonary bypass. IL-10 wasmeasured by enzyme immunoassay. The single nucleotide polymorphismat –1082 base pairs was detected by restriction fragmentlength polymorphism analysis. Post-bypass organ system dysfunctionwas defined prospectively. Results. IL-10 concentrations were increased 3 h afterbypass (P<0.0001) and were still increased at 24 h (P<0.0001).Homozygosity for the G allele was associated with lower median(range) maximal IL-10 levels at 3 h (44 (13–136)pg ml^–1) compared with the A allele (118 (39–472)pg ml^–1; P=0.042). Those patients who developed atleast one organ dysfunction (n=33) had higher IL-10 levels 3 hafter surgery (242 (18–694) pg ml^–1) comparedwith those without organ dysfunction (77 (7–586) pg ml^–1;P=0.001, n=117). Conclusions. The G allele of the –1082 base pair singlenucleotide polymorphism in the IL-10 gene is associated withlower IL-10 release after cardiopulmonary bypass. High levelsof IL-10 secretion are associated with organ dysfunction 24 hafter surgery. Br J Anaesth 2003; 91: 424–6     

Volume kinetics of glucose 2.5% solution and insulin resistance after abdominal hysterectomy

Background. We hypothesized that volume kinetics can be usedto predict the rate of infusion of glucose 2.5% solution requiredto yield any predetermined plasma glucose level and degree ofplasma dilution during the postoperative period. Methods. In 15 women, mean age 50 yr (range 37–63), 2days after an abdominal hysterectomy, a volume kinetic analysiswas performed on an i.v. infusion of 12.5 ml kg^–1 (900ml) of glucose 2.5% given over 45 min. The insulin resistancewas measured by a glucose clamp, and it was compared with dailybioimpedance analyses, which indicated the hydration of theintra/extracellular body fluid spaces. Results. The clearance of glucose was 0.42 litre min^–1(0.60 litre min^–1 is normal) while the other five parametersin the kinetic model were similar to those obtained in healthyvolunteers. Computer simulations indicated that in a 70-kg female,at steady state, the rate of infusion (ml min^–1) shouldbe three times the allowed increase in plasma glucose (mmollitre^–1). To maintain a predetermined plasma dilutionthe corresponding rate factor was 160. The glucose uptake duringclamping was 3.9 mg kg^–1 min^–1 (7.0 is normal),which, during the second day after hysterectomy, correlatedwith the dehydration of the intracellular space (r=0.77; P<0.002)and with the protein catabolism as indicated by the urinaryexcretion of 3-methylhistidine (r=–0.76, P<0.002). Conclusion. The anaesthetist can prescribe postoperative administrationof glucose 2.5% to reach any desired plasma glucose level anddilution by using the two presented nomograms. Insulin resistancecorrelated with intracellular dehydration and protein catabolism.     

Halothane enhances dopamine metabolism at presynaptic sites in a calcium-independent manner in rat striatum

Background. We have previously reported that halothane anaesthesiaincreases the extracellular concentration of dopamine (DA) metabolitesin the rat striatum with no change in DA. Although the metabolismof catecholamines is a source of oxidative stress, there islittle information about DA metabolism and anaesthesia. We assessedthe mechanism(s) of enhanced DA metabolism induced by halothane. Methods. Microdialysis probes were implanted into male Sprague–Dawleyrats and perfused with artificial cerebrospinal fluid (CSF).The dialysate was injected directly into an HPLC every 20 min.Each group of rats (n=5–7) was administered saline, apomorphine100 µg kg^–1, pargyline 7.5 or 75 mg kg^–1,reserpine 2 mg kg^–1 or -methyl-p-tyrosine (AMPT) 250 mgkg^–1. Another set of rats was perfused with artificialCSF containing tetrodotoxin (TTX) 1 µM or calcium-freeCSF containing 10 mM EGTA. Rats were anaesthetized with halothane0.5 or 1.5% 1 h after pharmacological treatments. Results. In rats pretreated with apomorphine, despite a decreasein DA concentration, halothane induced a increase in DA metabolites.Pargyline (high dose) and reserpine completely and AMPT partiallyantagonized the increase in DA metabolites induced by halothaneanaesthesia. TTX perfusion reduced the increase in DA, whereascalcium-free CSF perfusion did not. Conclusions. Our data suggest that halothane accelerates DAmetabolism at presynaptic sites by releasing DA from reserpine-sensitivestorage vesicles to the cytoplasm in a calcium-independent manner.The metabolic oxidative stress of inhalation anaesthesia requiresfuture investigation.     

Renoprotective effect of COMP-angiopoietin-1 in db/db mice with type 2 diabetes

Background. Inflammatory processes have been recently seen asunderlying the pathogenesis of diabetic nephropathy. Angiopoietin-1(Ang1) plays essential roles in regulating vascular growth,development, maturation, permeability and inflammation. We havedeveloped a soluble, stable and potent Ang1 variant, cartilageoligomeric matrix protein (COMP)-Ang1. Methods. In this study, db/db mice were treated with recombinantadenovirus expressing either COMP-Ang1 or LacZ. Histology, inflammatory,metabolic, and fibrotic parameters and signalling pathway wereevaluated. Results. COMP-Ang1 reduced albuminuria and decreased mesangialexpansion, thickening of the glomerular basement membrane andpodocyte foot process broadening and effacement. COMP-Ang1 suppressedboth renal expression of intercellular adhesion molecule-1 andmonocyte chemoattractant protein-1 and monocyte/macrophage infiltrationin diabetic db/db mice. COMP-Ang1 also reduced renal tissuelevels of transforming growth factor-ß1 (TGF-ß1),-smooth muscle actin, fibronectin, as well as Smad 2/3 expression,but increased Smad 7 expression. In human umbilical vein endothelialcells (HUVECs) grown in high glucose concentrations of glucose,recombinant COMP-Ang1 protein decreased nuclear factor-B (NF-B)expression. COMP-Ang1-mediated inhibition of increased NF-B-DNAbinding in nuclear extracts from HUVECs grown in high glucosewas significantly blocked by soluble Tie2 receptor-Fc. In addition,COMP-Ang1 significantly decreased fasting blood glucose level,epididymal fat weight to body weight ratio, and epididymal adipocytesize in diabetic db/db mice. After intraperitoneal glucose challenge,COMP-Ang1 significantly lowered plasma glucose levels. However,there was no difference in serum insulin levels. Conclusion. We conclude that COMP-Ang1 delayed the fibroticchanges in the kidney of diabetic db/db mice through its anti-inflammatoryor metabolic effects.     

Anaesthetics and cardiac preconditioning. Part I. Signalling and cytoprotective mechanisms

Cardiac preconditioning represents the most potent and consistentlyreproducible method of rescuing heart tissue from undergoingirreversible ischaemic damage. Major milestones regarding theelucidation of this phenomenon have been passed in the lasttwo decades. The signalling and amplification cascades fromthe preconditioning stimulus, be it ischaemic or pharmacological,to the putative end-effectors, including the mechanisms involvedin cellular protection, are discussed in this review. Volatileanaesthetics and opioids effectively elicit pharmacologicalpreconditioning. Anaesthetic-induced preconditioning and ischaemicpreconditioning share many fundamental steps, including activationof G-protein-coupled receptors, multiple protein kinases andATP-sensitive potassium channels (K_ATP channels). Volatile anaestheticsprime the activation of the sarcolemmal and mitochondrial K_ATPchannels, the putative end-effectors of preconditioning, bystimulation of adenosine receptors and subsequent activationof protein kinase C (PKC) and by increased formation of nitricoxide and free oxygen radicals. In the case of desflurane, stimulationof - and ß-adrenergic receptors may also be of importance.Similarly, opioids activate - and -opioid receptors, and thisalso leads to PKC activation. Activated PKC acts as an amplifierof the preconditioning stimulus and stabilizes, by phosphorylation,the open state of the mitochondrial K_ATP channel (the main end-effectorin anaesthetic preconditioning) and the sarcolemmal K_ATP channel.The opening of K_ATP channels ultimately elicits cytoprotectionby decreasing cytosolic and mitochondrial Ca²⁺ overload. Br J Anaesth 2003; 91: 551–65     

Nitric oxide synthase is downregulated, while haem oxygenase is increased, in patients with septic shock

Background. The vasodilatation characteristic of human septicshock is conventionally attributed to increased nitric oxideproduction, primarily by extrapolation of animal and human invitro studies. There are no conclusive studies of human disease,and the cellular source of nitric oxide in human sepsis is notknown. Haem oxygenase is upregulated by oxidative stress, butlittle is known about haem oxygenase expression in human sepsis.Haem oxygenase may modulate nitric oxide production, and mayalso have a direct effect on vascular tone. Methods. Mesenteric arterial smooth muscle (ASM) (obtained duringlaparotomy) and peripheral blood mononuclear cells (PBMCs) wereobtained from patients with early septic shock and from controlpatients. mRNA levels were determined by real-time RT-PCR. Results. mRNA for inducible and endothelial nitric oxide synthasewas reduced in both ASM and PBMCs from septic patients. In contrast,inducible haem oxygenase mRNA was increased in sepsis in bothcell types. Conclusions. These results suggest that, rather than being induced,the enzymes which produce nitric oxide are reduced at this timepoint in human septic shock. Thus many of the in vitro modelsof sepsis studied to date may not fully replicate human disease.The increase in haem oxygenase expression confirms that thesecells have been subjected to oxidative stress in sepsis. Theactivity of induced haem oxygenase may limit nitric oxide production,while possibly causing vasodilation through production of carbonmonoxide.     

Effects of dexamethasone on clinical course,C-reactive protein,S100B protein and von Willebrand factor antigen after paediatric cardiac surgery

Background. Anti-inflammatory treatment with glucocorticoidsduring cardiopulmonary bypass can reduce inflammatory mediatorrelease, but the effects of glucocorticoid on outcome are controversial. Methods. We studied the effects of dexamethasone on clinicalcourse, C-reactive protein, von Willebrand factor antigen (vWf:Ag)and S100B in a randomized masked study of children after opencardiac surgery. Twenty children weighing >10 kg receiveddexamethasone (1 mg kg^–1) and 20 controls receivedsaline after induction of anaesthesia. We measured vWf:Ag asa marker of endothelial activation, S100B as a marker of cerebralprotein release and C-reactive protein as a marker of inflammatoryactivity. Oxygenation, body temperature, fluid balance, leucocyteand platelet counts, days in the intensive care unit (ICU) anddays on mechanical ventilation were noted. Results. Dexamethasone decreased C-reactive protein concentrationon the first postoperative day (P<0.05), but did not affectthe release of vWf:Ag or S100B. There was no significant differencein oxygenation, body temperature, fluid balance, leucocyte andplatelet counts, days in the ICU or days on mechanical ventilationbetween the placebo and dexamethasone-treated groups. Conclusion. Administration of dexamethasone before cardiopulmonarybypass for paediatric cardiac surgery decreased the inflammatoryresponse, but did not affect the immediate features after surgeryor changes in vWf:Ag or S100B. Br J Anaesth 2003; 90: 728–32     

Opposite effects of depressant and convulsant barbiturate stereoisomers on acetylcholine release from the rat hippocampus in vivo

Background. It has been shown that the R(–) isomer of1-methyl-5-phenyl-5-propyl barbituric acid (MPPB) induces lossof the righting reflex (LRR), while S(+)-MPPB causes pure excitatoryeffects, including convulsions, in vivo. Methods. We studied the effects of the depressant and convulsantMPPB stereoisomers on rat hippocampal acetylcholine (ACh) releasein vivo, using a brain microdialysis technique in freely movinganimals. Results. R(–)-MPPB 60 and 90 mg kg^–1 i.p. decreasedACh release from the rat hippocampus by 44.1 (8.2)% and 60.8(8.2)%, respectively. In the hippocampus, the local applicationof bicuculline, a -aminobutyric acid (GABA)_A receptor antagonist,1 µmol litre^–1 antagonized the inhibitory effectsof R(–)-MPPB 90 mg kg^–1 i.p. In contrast, R(–)-MPPB,S(+)-MPPB 60 and 90 mg kg^–1 i.p. increased ACh releaseto 151.8 (6.8)% and 169.6 (11.1)% of the basal release, respectively. Conclusions. Our results demonstrated that R(–)-MPPB decreased,while S(+)-MPPB increased, rat hippocampal ACh release and thatthe inhibitory effects of R(–)-MPPB may involve the GABA_Areceptor in vivo. These data imply that changes in hippocampalACh due to these agents may be related to their central inhibitoryand stimulatory actions in vivo. Br J Anaesth 2004; 92: 424–6     

Effects of endogenous and synthetic opioid peptides on neutrophil function in vitro

Background. Opioid peptides released from immunocytes duringinflammation and stress in critically ill patients are associatedwith an altered immune response. Moreover, concentrations ofopioid peptides are increased in peripheral blood and at thesites of inflammatory reactions. Methods. Using flow cytometric assay of whole human blood, weinvestigated direct effects of endogenous and synthetic opioidpeptides on surface expression of complement receptors CD35and CD11b/CD18 and Fcã receptor III CD16, and superoxideanion generation of neutrophils. Results. The endogenous opioid peptides ß-endorphin_1–31and met-enkephalin, representing the N-terminal fragment ofß-endorphin_1–31, and the synthetic opioid receptoragonists D-Ala₂-D-Leu₅-enkephalin and D-Pen₂-enkephalin producedconcentration-dependent stimulation of neutrophil activity.Incubation with met-enkephalin 10^–7 M or ß-endorphin_1–3110^–7 M led to an increase in receptor expression of upto 10% (met-enkephalin) and 15% (ß-endorphin_1–31).After incubation with D-Ala₂-D-Leu₅-enkephalin or D-Pen_2/5-enkephalin,receptor expression was increased by up to 30%. This correlatedwith concentration-dependent stimulation of the production ofreactive oxygen intermediates, as shown by an increase of upto 40% in oxidative burst activity. All effects were abolishedafter preincubation with naloxone or with the selective opioidantagonist naltrindole, whereas the selective µ receptorantagonist d-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH₂ showed onlypartial inhibitory effects. Conclusions. Our data suggest a opioid receptor-mediated stimulatoryeffect on neutrophil function. ß-Endorphin_27–31,the C-terminal fragment of ß-endorphin_1–31,did not alter neutrophil function, indicating that ß-endorphin_1–31mediates its effect on neutrophils via the N-terminal fragment.This study may contribute to a better understanding of neuroimmuneinteraction. Br J Anaesth 2003; 91: 546–50     

Release by hypoxia of a soluble vasoconstrictor from rabbit small pulmonary arteries

Background. Soluble pulmonary vasoconstrictors released in responseto hypoxia have been reported in pig and rat preparations, butnot in rabbit preparations. Methods. We used myography to evaluate the contribution of asoluble factor to constriction in rabbit small pulmonary arteries(external diameter 300–475 µm) exposed to 45 minhypoxia (PO₂=9 mm Hg). Results. Hypoxia produced gradually intensifying constriction.Return to euoxia (PO₂=145 mm Hg) for 30 min relaxed onlyapproximately 30% of the constriction, whereas elution of themyograph bath yielded full relaxation. Reapplication of theeluent gradually restored the constriction to its pre-elutionlevel over a 30-min period. Conclusions. In this closed system, a soluble factor contributessubstantially to hypoxic pulmonary vasoconstriction. Br J Anaesth 2003; 91: 592–4     

In vivo effect of haemodilution with saline on coagulation: a randomized controlled trial

Background. Previous studies have shown that 10–30% haemodilutionwith crystalloid may induce a hypercoagulable state demonstrableby using the Thrombelastograph^® (TEG). While most are invitro studies, the few in vivo studies are limited by confoundingsurgical or ‘environmental’ factors. We conductedthis randomized controlled study to evaluate the coagulationchanges associated with in vivo haemodilution. Methods. Twenty patients undergoing major hepatobiliary surgerywere randomly allocated to one of two study groups. Group H(n=10) had 30% blood volume withdrawn over 30 min and replacedwith saline. Group C (n=10) did not have any blood withdrawn.Blood samples were taken in both groups at 10, 20 and 30 min.Native TEG, complete blood count, coagulation profile, fibrinogen,antithrombin III, protein C and thrombin–antithrombincomplex concentrations were measured. Results. Compared with Group C, Group H patients had significantlygreater shortening of r-time at 30 min (–30% vs +36%),greater shortening of k-time at all time points (–36%vs +17% at 10 min; –37% vs +44% at 20 min; –45%vs +49% at 30 min), and greater widening of     

The effects of propofol on neutrophil function, lipid peroxidation and inflammatory response during elective coronary artery bypass grafting in patients with impaired ventricular function

Background. Coronary artery bypass grafting (CABG) with cardiopulmonarybypass elicits a potent reperfusion injury and inflammatoryresponse, more intense in patients with impaired myocardialfunction. Propofol has antioxidant properties which may attenuatesuch a response. Methods. In total, 27 patients with impaired left ventricularfunction undergoing CABG were randomly allocated to receiveeither target-controlled infusion propofol (P) or saline (S)immediately before aortic cross-clamp release until 4 h afterreperfusion. Troponin-I, Urinary 8-epi PGF-2 isoprostane, coronarysinus and systemic malondialdehyde concentrations, Interleukin-6(IL-6), -8 and -10 concentrations and leucocytes function studies(neutrophil respiratory burst, phagocytosis, CD-11b and CD-18expression) were measured. Results. Propofol decreased MDA coronary sinus concentrationat 1, 3 and 5 min after reperfusion (P<0.01); 60 min afterreperfusion a significant difference between the two groupsin systemic MDA concentrations was also seen. IL-6 concentrationincreases were significantly greater in Group S than Group P,4 h after reperfusion [1118 (1333) pg ml^–1 vs 228 (105)pg ml^–1, P<0.01]. Serum IL-8 concentrations did notincrease significantly in either group. Compared with baselinevalues IL-10 concentrations decreased after reperfusion butthe values were higher in the propofol group than in the controlgroup [22 (16) vs 11 (4) pg ml^–1, P<0.05]. No differencein leucocyte function or urinary isoprostane concentrationswas demonstrated. Conclusion. Propofol attenuates free-radical-mediated lipidperoxidation and systemic inflammation in patients with impairedmyocardial function undergoing CABG.     

Comparison of L-bupivacaine 0.75% and lidocaine 2% with bupivacaine 0.75% and lidocaine 2% for peribulbar anaesthesia

Background. L-Bupivacaine has a safer side-effect profile thanbupivacaine. We compared the efficacy of a mixture of L-bupivacaine0.75% and lidocaine 2% with bupivacaine 0.75% and lidocaine2% for peribulbar anaesthesia in cataract surgery. Methods. Ninety patients were allocated randomly to receive8 ml of a mixture of equal parts of bupivacaine 0.75% and lidocaine2% or an equal volume of L-bupivacaine and lidocaine 2%. Hyaluronidase15 IU ml^–1 was added to both solutions. Results. There were significant differences between the groupsin clinical end-points. The median time at which the block wasadequate to start surgery was 4 min (interquartile range4–8 min) in the bupivacaine group and 8 min (5–12min) in the L-bupivacaine group (P=0.002). Median ocular andeyelid movement scores were similarly significantly decreasedin the bupivacaine group compared with the L-bupivacaine groupat all times (P0.03). There was no difference between groupsin the incidence of minor complications. Conclusions. A mixture of bupivacaine 0.75% and lidocaine 2%provides faster onset time than a mixture of L-bupivacaine 0.75%and lidocaine 2%. Br J Anaesth 2003; 90: 512–14     

Influence of sepsis on minimum alveolar concentration of desflurane in a porcine model

The effect of sepsis on the minimum alveolar concentration ofdesflurane (MAC_DES) in humans and other animals has not beenreported previously. The aim of this study was to test the hypothesisthat sepsis might alter MAC_DES in a normotensive septic porcinemodel. Twenty-four young healthy pigs were premedicated withketamine 10 mg kg^–1 i.m and then anaesthesia was establishedwith propofol 3 mg kg^–1 and the trachea was intubated.Baseline MAC_DES in each pig was evaluated by pinching with ahaemostat applied for 1 min to a rear dewclaw. MAC_DES was determinedby changing desflurane concentrations stepwise until purposefulmovement appeared. Pigs were randomly assigned to two groupsof 12 animals: the saline group received a 1 h i.v. infusionof saline solution while the sepsis group received a 1 h i.v.infusion of live Pseudomonas aeruginosa. Epinephrine and hydroxyethylstarchwere used to maintain normotensive and normovolaemic haemodynamicstatus. In both groups, MAC_DES was evaluated 5 h after infusion.Significant increases in heart rate, cardiac output, mean pulmonaryartery pressure and pulmonary vascular resistance occurred inthe sepsis group. MAC_DES was 9.2% (95% confidence interval (CI)6.8–10.6%) for the saline group and 6.7% (95% CI: 4.7–10.4)for the sepsis group (P<0.05). These data indicate that MAC_DESis significantly decreased in this normotensive hyperkineticseptic porcine model. Br J Anaesth 2001; 86: 280–3     

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-     

Efficacy of three doses of tramadol with bupivacaine for caudal analgesia in paediatric inguinal herniotomy

Background. This study was designed to evaluate the analgesicefficacy of three doses of tramadol, administered caudally withbupivacaine, in providing postoperative pain relief in children. Methods. Eighty children, aged between 2 and 8 yr, undergoinginguinal herniotomy were randomly allocated to receive bupivacaine0.25% 0.75 ml kg^–1 (Group B; n=20), bupivacaine 0.25%0.75 ml kg^–1 with tramadol 1 mg kg^–1 (Group BT1;n=20), bupivacaine 0.25% 0.75 ml kg^–1 with tramadol 1.5mg kg^–1 (Group BT1.5; n=20), or bupivacaine 0.25% 0.75ml kg^–1 with tramadol 2 mg kg^–1 (Group BT2; n=20)by the caudal route immediately after induction of general anaesthesia.Heart rate, arterial pressure and oxygen saturation were monitored.Postoperative pain was assessed at regular intervals for 24h using All India Institute of Medical Sciences pain score.Analgesia was supplemented whenever pain score was 4. Durationof analgesia and requirement for additional analgesics was noted. Results. Duration of analgesia was longer in Group BT2 [(mean(SD) 12 (0.9) h] compared with Group B [4 (1) h], Group BT1[8 (0.9) h], or Group BT1.5 [11 (1) h]; all P<0.001. Totalconsumption of rescue analgesic was significantly lower in groupBT2 compared with other groups (P<0.001). There were no significantchanges in heart rate, arterial pressure and oxygen saturationbetween groups. Adverse effects were not observed. Conclusions. Caudal tramadol 2 mg kg^–1, combined withbupivacaine 0.25% 0.75 ml kg^–1, provided longer durationof postoperative analgesia and reduced requirement for rescueanalgesic compared with tramadol 1 mg kg^–1 or 1.5 mg kg^–1in children undergoing inguinal herniotomy.     

Complete airway obstruction in a ventilated patient after oesophageal dilatation

A case of instrumental perforation of the oesophagus is presented.This caused systemic sepsis, requiring tracheal intubation andpositive pressure ventilation. Sudden unexpected life-threateningairway obstruction was caused by distal tracheal compressionby a peritracheal abscess. The aetiology and management of distaltracheal obstruction is discussed. Br J Anaesth 2002; 89: 517–19     

Predictive performance of computer-controlled infusion of remifentanil during propofol/remifentanil anaesthesia

Background. The predictive performance of the available pharmacokineticparameter sets for remifentanil, when used for target-controlledinfusion (TCI) during total i.v. anaesthesia, has not been determinedin a clinical setting. We studied the predictive performanceof five parameter sets of remifentanil when used for TCI ofremifentanil during propofol anaesthesia in surgical patients. Methods. Remifentanil concentration–time data that hadbeen collected during a previous pharmacodynamic interactionstudy in 30 female patients (ASA physical status I, aged 20–65 yr)who received a TCI of remifentanil and propofol during lowerabdominal surgery were used in this evaluation. The remifentanilconcentrations predicted by the five parameter sets were calculatedon the basis of the TCI device record of the infusion rate–timeprofile that had actually been administered to each individual.The individual and pooled bias [median performance error (MDPE)],inaccuracy [median absolute performance error (MDAPE)], divergenceand wobble of the remifentanil TCI device were determined fromthe pooled and intrasubject performance errors. Results. A total of 444 remifentanil blood samples were analysed.Blood propofol and remifentanil concentrations ranged from 0.5to 11 µg ml^–1 and 0.1 to 19.6 ng ml^–1respectively. Pooled MDPE and MDAPE of the remifentanil TCIdevice were –15 and 20% for the parameter set of Mintoand colleagues (Anesthesiology 1997; 86: 10–23), 1 and21%, –6 and 21%, and –6 and 19% for the three parametersets described by Egan and colleagues (Anesthesiology 1996;84: 821–33, Anesthesiology 1993; 79: 881–92, Anesthesiology1998; 89: 562–73), and –24 and 30% for the parameterset described by Drover and Lemmens (Anesthesiology 1998; 89:869–77). Conclusions. Remifentanil can be administered by TCI with acceptablebias and inaccuracy. The three pharmacokinetic parameter setsdescribed by Egan and colleagues resulted in the least biasand best accuracy. Br J Anaesth 2003; 90: 132–41