Haemodynamic and renal effects of intravenous enalaprilat during coronary artery bypass graft surgery in patients with ischaemic heart dysfunction

Renal dysfunction occurring after open heart surgery is multifactorialin origin but activation of the renin–angiotensin systemmay have a prominent role. Fourteen patients with ischaemicheart dysfunction scheduled for elective coronary artery bypassgraft (CABG) surgery were allocated to a treatment group [enalaprilatfor 2 days; ACEI (angiotensin-converting enzyme inhibitor) group,n=7] or a control group (n=7). The cardiac index was significantlyhigher in ACEI-treated patients than in the controls beforeand after cardiopulmonary bypass (CPB) (P<0.05) and on postoperativeday 2 (P<0.05). The systemic vascular resistance wassignificantly lower in the ACEI-treated patients than in thecontrols before and after CPB (P<0.05). Renal plasma flow,measured as [¹³¹I]orthoiodohippuran clearance (Cl_H), was higherin the ACEI group than in the control group before CPB, as wasendogenous creatinine clearance after CPB (P<0.05). On post-operativeday 7, Cl_H was significantly higher in the ACEI group thanin the control group (P<0.05). Plasma renin activity andvasopressin concentration increased in both groups during CPB(P<0.05). The study demonstrates that administration of ani.v. ACEI, enalaprilat, improves cardiac output during CABGsurgery in patients with ischaemic heart dysfunction. Moreover,renal perfusion was better maintained during surgery, and thiseffect was sustained up to post-operative day 7. Br J Anaesth 2001; 86: 169–75     

Renal function and cardiopulmonary bypass in pediatric cardiac surgical patients

We studied prospectively the perioperative changes of renal function in nine children undergoing cardiac surgery with cardiopulmonary bypass (CPB). Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured with inulin and ¹³¹I-hippuran clearances before CPB, during hypo and normothermic CPB, following sternal closure and 1 h postoperatively. Urinary alpha glutathione S-transferase (alpha GS-T) was measured pre- and postoperatively as a marker for tubular cellular damage. Plasma and urine creatinine and electrolytes were measured. Free water, osmolal and creatinine clearances, as well as fractional excretion of sodium (FeNa) and potassium transtubular gradient (TTKG) were calculated. GFR was normal before and after surgery. ERPF was low before and after surgery; it increased significantly immediately after CPB. Filtration fraction (FF) was abnormally elevated before and after surgery; however, a significant decrease during normothermic CPB and sternal closure was found. Alpha GS-T presented a moderate, but nonsignificant increase postoperatively. FeNa also increased in this period, but not significantly. Creatinine, osmolal, free water clearances, as well as TTKG, were normal in all patients pre- and postoperatively. We conclude that there is no evidence of clinically significant deterioration of renal function in children undergoing repair of cardiac lesions under CPB. Minor increases of alpha GS-T in urine postoperatively did not confirm cellular tubular damage. There was no tubular dysfunction at that time.Supported by grant 1030645 from FONDECYT.     

Lack of renoprotective effect of i.v. N-acetylcysteine in patients with chronic renal failure undergoing cardiac surgery

Background. Pre-existing chronic renal failure is a significantrisk factor for acute renal failure (ARF) after cardiac surgery.N-acetylcysteine (NAC) has been shown to prevent contrast media-inducedARF. Our objective was to evaluate whether i.v. NAC has renoprotectiveeffects in patients with mild renal failure undergoing cardiacsurgery. Methods. In this prospective, randomized, double-blind study,80 patients with mild to moderate renal failure undergoing electiveheart surgery with cardiopulmonary bypass were recruited. Allreceived either i.v. NAC (n=38) or placebo (n=39) at inductionof anaesthesia and then up to 20 h. Urine N-acetyl-ß-D-glucosaminidase(NAG) and urine creatinine ratio, plasma creatinine, and serumcystatin C levels indicated renal function. Results. Levels of urinary NAG/creatinine ratio, plasma creatinineand serum cystatin C did not significantly differ between NACand placebo groups during five postoperative days. Urine NAG/creatinineratio increased over 30% in 100% of patients in the NAC groupvs 92.3% in the placebo group (P=0.081). Plasma creatinine increasedby 25% from baseline or over 44 µmol litre^–1 in42.1% in NAC group vs 48.7% in placebo group (P=0.560). Serumcystatin C exceeded 1.4 mg litre^–1 in 78.9% in NAC groupvs 61.5% in placebo group (P=0.096). Conclusions. Prophylactic treatment with i.v. N-acetylcysteinehad no renoprotective effect in patients with pre-existing renalfailure undergoing cardiac surgery.     

Effect of rofecoxib on platelet aggregation and blood loss in gynaecological and breast surgery compared with diclofenac

Background. Non-selective cyclooxygenase (COX) inhibitors ornon-steroidal anti- inflammatory drugs (NSAIDs) are frequentlyomitted for perioperative pain relief because of potential side-effects.COX-2-selective inhibitors may have a more favourable side-effectprofile. This study tested the hypothesis that the COX-2-selectiveinhibitor rofecoxib has less influence on platelet functionthan the NSAID diclofenac in gynaecological surgery. In addition,analgesic efficacy and side-effects of the two drugs were compared. Methods. In this single-centre, prospective, double-blind, activecontrolled study, women undergoing vaginal hysterectomy (n=25)or breast surgery (n=25) under general anaesthesia receivedpreoperatively 50 mg of rofecoxib p.o. followed 8 and 16 h laterby two doses of placebo or three doses of diclofenac 50 mg p.o.at the same time points. We assessed arachidonic acid-stimulatedplatelet aggregation before and 4 h after the first dose ofstudy medication, estimated intraoperative blood loss, and haemoglobinloss until the first morning after surgery. Analgesic efficacy,use of rescue analgesics, and side-effects were also recorded. Results. In the rofecoxib group, stimulated platelet aggregationwas disturbed less (P=0.02), and estimated intraoperative bloodloss (P=0.01) and the decrease in haemoglobin were lower (P=0.01).At similar pain ratings, the use of anti-emetic drugs was lessin the rofecoxib group (P=0.03). Conclusion. Besides having a smaller effect on platelet aggregation,one oral dose of rofecoxib 50 mg given before surgery providedpostoperative analgesia similar to that given by three dosesof diclofenac 50 mg and was associated with less use of anti-emeticsand less surgical blood loss in gynaecological surgery comparedwith diclofenac. Br J Anaesth 2004; 92: 523–31     

Cerebral ischaemia during cardiac surgery in children detected by combined monitoring of BIS and near-infrared spectroscopy

Background. Children frequently suffer transient cerebral ischaemiaduring cardiac surgery. We measured cerebral ischaemia in childrenduring cardiac surgery by combining two methods of monitoring. Methods. We studied 65 children aged between 5 months and 17yr having surgery to correct non-cyanotic heart disease usinghypothermic cardiopulmonary bypass (CPB). During surgery, wemeasured the Bispectral Index (BIS) and regional cerebral haemoglobinoxygen saturation (Sr_O2) with near-infrared spectroscopy (NIRS).Cerebral ischaemia was diagnosed if both Sr_O2 and BIS decreasedabruptly when acute hypotension occurred. In each patient, therelationship between Sr_O2 and arterial blood pressure (AP) wasindicated by a plot of mean Sr_O2 against simultaneous mean AP. Results. We noted 72 episodes of cerebral ischaemia in 38 patients.Sixty-three ischaemic events were during CPB. Cerebral ischaemiawas less frequent in older patients. Cerebral ischaemia wasmore common and more frequent in children under 4 yr old. Haematocritduring CPB was lower and Sr_O2 was more dependent on AP in childrenunder 4 yr. Conclusions. Children less than 4 yr of age are more likelyto have cerebral ischaemia caused by hypotension during cardiacsurgery. Ineffective cerebral autoregulation and haemodilutionduring CPB may be responsible. Br J Anaesth 2004: 92: 662–9     

Serum S100 protein as a marker of cerebral damage during cardiac surgery

The identification of a serum marker to assist in the diagnosisof cerebral injury after cardiac surgery is potentially useful.S100 protein is an early marker of cerebral damage. It is releasedafter cardiac surgery performed under cardiopulmonary bypass(CPB). Its level is correlated with the duration of CPB, deepcirculatory arrest and aortic cross-clamping. Increased levelsof S100 protein are correlated with the age of the patient andthe number of microemboli, especially during aortic cannulation.Perioperative cerebral complications such as stroke, delayedawakening and confusion are associated with increased levelsof S100 protein directly after bypass and from 15 to 48 hafter it. In addition, increased levels of S100 protein arerelated to neuropsychological dysfunction after cardiac surgery.S100 protein has early and late release patterns after CPB;the early pattern may be due to sub-clinical brain injury. Thelate release pattern may be due to perioperative cerebral complications.Patients undergoing intracardiac operations combined with coronaryartery bypass surgery are more susceptible to brain injury andhave higher levels of S100 after CPB. Furthermore, adults andchildren undergoing deep circulatory arrest are more susceptibleto brain injury, in terms of higher S100 protein release afterCPB. Serum S100 protein levels are reduced after using arterialline filtration and covalent-bonded heparin to coat the innersurface of the CPB circuit. Br J Anaesth 2000; 85: 287–98     

Prevention of postoperative nausea and vomiting after spinal morphine for Caesarean section: comparison of cyclizine,dexamethasone and placebo

Background. Low-dose intrathecal (spinal) morphine (0.1–0.2mg) for Caesarean section delivers excellent postoperative analgesiabut is associated with significant nausea and vomiting. We comparedthe antiemetic efficacy of cyclizine, dexamethasone, and placeboin this clinical setting. Methods. Ninety-nine women undergoing elective Caesarean sectionunder spinal anaesthesia were allocated randomly, in a double-blindstudy design, to receive either cyclizine 50 mg, dexamethasone8 mg, or placebo as a single-dose infusion in saline 0.9%, 100ml on completion of surgery. Spinal anaesthesia consisted of:hyperbaric bupivacaine 0.5%, 2.0 ml; fentanyl 10 µg; andspinal morphine 0.2 mg. The primary outcome measure was theincidence of nausea. Results. The incidence of nausea was significantly less in patientsreceiving cyclizine compared with dexamethasone and placebo(33 vs 60 and 67%, respectively, P<0.05). Severity of nauseaand number of vomiting episodes were also less at 3–6h in cyclizine patients. Overall satisfaction with postoperativecare at 24 h, expressed on a 100 mm visual analogue scale, wasgreater in cyclizine [78 (28)] than either dexamethasone [58(31), P=0.03] or placebo [51 (28), P=0.008]. Conclusion. We conclude that following spinal morphine 0.2 mgand fentanyl 10 µg analgesia for Caesarean section, cyclizine50 mg i.v. reduces the incidence of nausea compared with dexamethasone8 mg i.v. or placebo. It also lessens the severity of nauseaand vomiting, and increases maternal satisfaction in the earlypostoperative period. Br J Anaesth 2003; 90: 665–70     

Increased carbon dioxide absorption during retroperitoneal laparoscopy

Background. Retroperitoneoscopy for renal surgery is now a commonprocedure. We compared carbon dioxide absorption in patientsundergoing retroperitoneoscopy for adrenal or renal surgerywith that of patients undergoing laparoscopic cholecystectomy. Methods. We measured carbon dioxide elimination with a metabolicmonitor in 30 anaesthetized patients with controlled ventilation,undergoing retroperitoneoscopy (n=10), laparoscopy (n=10) ororthopaedic surgery (n=10). Results. Carbon dioxide production increased by 38, 46 and 63%at 30, 60 and 90 min after insufflation (P<0.01) in patientshaving retroperitoneoscopy. Carbon dioxide production (mean(SD)) increased from 92 (21) to 150 (43) ml min^–1 m^–260–90 min after insufflation and remained increased afterthe end of insufflation. During laparoscopy, V^·_CO2 increasedless (by 15%) (P<0.05 compared with retroperitoneoscopy)and remained steady throughout the procedure. Conclusion. Retroperitoneal carbon dioxide insufflation causesmore carbon dioxide absorption than intraperitoneal insufflation,and controlled ventilation should be increased if hypercapniashould be avoided. Br J Anaesth 2003; 91: 793–6     

Glucose,insulin and potassium for heart protection during cardiac surgery

Background. Coronary artery bypass grafting with hypothermiccardiac arrest and cardiopulmonary bypass (CPB) is associatedwith myocardial injury. Our study investigated whether an infusionof glucose, insulin and potassium (GIK) during elective coronaryartery bypass surgery decreases myocardial cell death. Methods. We measured cardiac troponin I (cTnI), a myofibrillarstructural protein, which is a sensitive and specific indicatorof myocytic injury. With ethics committee approval, 42 patientswere enrolled into a randomized, prospective, double-blindedstudy. In the GIK group, 500 ml of 50% dextrose solutioncontaining 100 IU insulin and potassium 80 mmol was infusedat the rate of 0.75 ml kg^–1 h^–1.Patients in the non-GIK group received 5% dextrose solutionat the same rate. Arterial blood samples were taken before inductionof anaesthesia, after removal of the aortic clamp and 6 and12 h after CPB. Results. In both groups there was an increase in cTnI concentration(P<0.05), which was greatest about 6 h after CPB. Atno time did the cTnI concentration differ between the two groups. Conclusion. The results suggest that GIK does not decrease theirreversible myocardial damage associated with routine coronaryartery bypass surgery. Br J Anaesth 2002; 88: 489–95     

Effect of obesity and site of surgery on perioperative lung volumes

Background. Although obese patients are thought to be susceptibleto postoperative pulmonary complications, there are only limiteddata on the relationship between obesity and lung volumes aftersurgery. We studied how surgery and obesity affect lung volumesmeasured by spirometry. Methods. We prospectively studied 161 patients having eitherbreast surgery (Group A, n=80) or lower abdominal laparotomy(Group B, n=81). Premedication and general anaesthesia werestandardized. Spirometry was measured with the patient supine,in a 30° head-up position. We measured vital capacity (VC),forced vital capacity, peak expiratory flow and forced expiratoryvolume in 1 s at preoperative assessment (baseline), after premedication(before induction of anaesthesia) and 10–20 min, 1 h and3 h after extubation. Results. Baseline spirometric values were all within the normalrange. All perioperative values decreased significantly withincreasing body mass index (BMI). The greatest reduction ofmean VC (expressed as percentage of baseline values) occurredafter extubation, and was more marked after laparotomy thanafter breast surgery (23 (SD 14)% vs 20 (14)%). Consideringpatients according to BMI (<25, 25–30, >30), VCdecreased after surgery by 12 (7)%, 24 (8)% and 40 (10)%, respectively.VC recovered more rapidly in Group A. Conclusion. Postoperative reduction in spirometric volumes wasrelated to BMI. Obesity had more effect on VC than the siteof surgery. Br J Anaesth 2004; 92: 202–7     

No effect of cardiopulmonary bypass on hypnosis in patients anaesthetized with propofol and alfentanil

Background. The effect of cardiopulmonary bypass (CPB) on thelevel of anaesthetic depth has not been studied previously ina randomized way. Methods. We assessed the effect of CPB on the propofol neededto maintain a fixed bispectral index score, and on the recoveryfrom anaesthesia in 22 patients undergoing coronary artery bypassgraft surgery with CPB (on-pump) compared with 18 patients operatedon without CPB (off-pump). Anaesthesia was induced and maintainedwith propofol and alfentanil. Throughout the procedure, theinfusion rate of propofol was adjusted to keep the BIS valueat 40 ± 5. Results. With the off-pump technique, the duration of surgeryand anaesthetic administration were significantly greater. Theneed for propofol in proportion to time was exactly the samein both groups. During anaesthesia and the first 3 h thereafter,the BIS recordings were similar in both groups. No differenceswere detected in the time to awakening or tracheal extubation. Conclusions. CPB does not affect propofol requirements or immediatepostoperative recovery compared with the off-pump technique. Br J Anaesth 2004; 92: 137–9     

Cost-effectiveness of three combinations of antiemetics in the prevention of postoperative nausea and vomiting

Background. This study compares the cost-effectiveness of threecombinations of antiemetics in the prevention of postoperativenausea and vomiting (PONV). Methods. We conducted a prospective, double-blind study. NinetyASA I–II females, 18–65 yr, undergoing general anaesthesiafor major gynaecological surgery, with standardized postoperativeanalgesia (intrathecal 0.2 mg plus i.v. PCA morphine), wererandomly assigned to receive: ondansetron 4 mg plus droperidol1.25 mg after induction and droperidol 1.25 mg 12 h later (Group1); dexamethasone 8 mg plus droperidol 1.25 mg after inductionand droperidol 1.25 mg 12 h later (Group 2); ondansetron 4 mgplus dexamethasone 8 mg after induction and placebo 12 h later(Group 3). A decision analysis tree was used to divide eachgroup into nine mutually exclusive subgroups, depending on theincidence of PONV, need for rescue therapy, side effects andtheir treatment. Direct cost and probabilities were calculatedfor each subgroup, then a cost-effectiveness analysis was conductedfrom the hospital point of view. Results. Groups 1 and 3 were more effective (80 and 70%) thanGroup 2 (40%, P=0.004) in preventing PONV but also more expensive.Compared with Group 2, the incremental cost per extra patientwithout PONV was €6.99 (95% CI, –1.26 to 36.57) forGroup 1 and €13.55 (95% CI, 0.89–132.90) for Group3. Conclusion. Ondansetron+droperidol is cheaper and at least aseffective as ondansetron+ dexamethasone, and it is more effectivethan dexamethasone+droperidol with a reasonable extra cost. Br J Anaesth 2003; 91: 589–92     

Editorial IV: physical and pharmacological restraint of critically ill patients: clinical facts and ethical considerations

Background. Leucocyte-depleting arterial line filters have notdramatically improved lung function after cardiopulmonary bypass(CPB), but patients with pre-existing lung dysfunction may benefitfrom their use. Methods. We randomized 32 patients with mild lung dysfunctionhaving elective first-time coronary revascularization to eithera leucocyte depleting or a standard 40-mm arterial line filterduring CPB. The alveolar arterial oxygenation index was calculatedbefore and 5 min after CPB, then at 1, 2, 4, 8, and 18 h aftersurgery. Time to extubation on the ITU was recorded. Preoperative,immediate postoperative, and 24 h postoperative chest x-rayswere scored for extravascular lung water. Results. Postoperative alveolar–arterial oxygenation indiceswere better in the patients who received leucocyte depletionduring CPB (1.65±0.96 in the study group vs 2.90±1.72in the control group, P<0.05). The duration of postoperativemechanical ventilation was less in the leucocyte-depleted group(4.8±2.1 vs 8.3±4.7 h in the control group, P<0.05).The extravascular lung water scores immediately postoperativelywere 13.0±8.6 in the study group vs 19.6±10.8in the control group (P=0.04), and at 24 h postoperatively,9.7±7.7 vs 15.2±9.9 for controls. Conclusions. For patients with mild lung dysfunction, a leucocyte-depletingarterial line filter improves postoperative oxygenation, reducesextravascular lung water accumulation, and reduces time on artificialventilator after CPB. There may be an economic argument forthe routine use of leucocyte-depleting filters for every patientduring CPB.     

Plasma propofol concentration and EEG burst suppression ratio during normothermic cardiopulmonary bypass

Background. During cardiopulmonary bypass (CPB), several factorsaffect drug disposition and action. This topic has not beenstudied extensively during normothermic CPB. In this study,we related propofol dose to plasma propofol concentration andburst suppression of the EEG during normothermic bypass. Methods. After institutional approval and informed consent,45 patients having cardiac surgery were assigned randomly toreceive propofol infusions at 4 (Group A), 5 (Group B) and 6(Group C) mg kg^–1 h^–1 during normothermic CPB. Inall patients, small to moderate doses of fentanyl were alsoadministered. Plasma propofol concentration and burst suppressionratio (BSR) were measured at the following times: (1) 10 minbefore CPB, (2) 10 min after the start of CPB, (3) 30 min afterthe start of the CPB, (4) just after aortic declamping, and(5) 60 min after CPB. Results. At baseline, plasma propofol concentrations were similaramong the three groups. After the start of CPB, the concentrationsof propofol decreased significantly by 41, 35, and 30% of controlvalues in Groups A, B, and C, respectively. In Group A, theconcentration of propofol during CPB remained unchanged at lessthan the concentration before bypass. In Groups B and C, plasmapropofol concentrations gradually increased during CPB to thepre-bypass concentrations. In Group A, BSR values did not changesignificantly during CPB. In Groups B and C, BSR values graduallyincreased and became significantly greater than baseline values.No patient reported intraoperative awareness. Conclusion. The pharmacokinetics and pharmacodynamics of propofolchange during normothermic CPB. During normothermic CPB, theefficacy of propofol may be enhanced compared with before CPB. Br J Anaesth 2003; 90: 122–6     

Pharmacokinetics of remifentanil and its major metabolite, remifentanil acid, in ICU patients with renal impairment

Background. The pharmacokinetics of remifentanil, an opioidanalgesic metabolized by non-specific esterases, and its principalmetabolite, remifentanil acid (RA), which is excreted via thekidneys, were assessed as part of an open-label safety studyin intensive care unit (ICU) patients with varying degrees ofrenal impairment. Methods. Forty adult ICU patients with normal/mildly impairedrenal function (creatinine clearance [CL_cr] 62.9 (SD) 14.5 mlmin^–1; n=10) or moderate/severe renal impairment (CL_cr14.7 (15.7) ml min^–1; n=30) were included. Remifentanilwas infused for up to 72 h, at a starting rate of 6–9µg kg^–1 h^–1 titrated to achieve a target sedationlevel, with additional propofol (0.5 mg kg^–1 h^–1)if required. Intensive arterial sampling was performed for upto 72 h after infusion. Pharmacokinetic parameters obtainedby simultaneous modelling of remifentanil and RA data were statisticallycompared between the two groups. Results. Remifentanil pharmacokinetics were not significantlyaffected by renal status. RA clearance in the moderate/severegroup was reduced to about 25% that of the normal/mild group(41 (29) vs 176 (49) ml kg^–1 h^–1, P<0.0001).Metabolic ratio, a predictor of the ratio of RA to remifentanilconcentrations at steady state, was approximately eight-foldhigher in the moderate/severe group relative to the normal/mildgroup (116 (110) vs 15 (4), P<0.0001). Maximum RA levelsapproached 700 ng ml^–1 in the moderate/severe group. Conclusions. Although RA accumulates in patients with moderate/severerenal impairment, pharmacokinetic modelling predicts that RAconcentrations during a 9 µg kg^–1 h^–1 remifentanilinfusion for up to 15 days would not exceed those reported inthe present study, for which no associated prolongation of µ-opioideffects was observed. Br J Anaesth 2004; 92: 493–503     

Efficacy of aminocaproic, tranexamic acids in the control of bleeding during total knee replacement: a randomized clinical trial

Background. Risks and costs of allogeneic blood transfusionsmandate strategies to reduce blood loss in surgery. The objectiveof this study was to assess the efficacy of antifibrinolytictreatment in reducing perioperative blood loss during totalknee replacement. Methods. A double-blind, randomized and placebo-controlled clinicaltrial was carried out on 127 patients undergoing total kneereplacement. Patients in the study group received tranexamicacid 10 mg kg^–1 i.v. just before the tourniquet was deflatedand 3 h later, or epsilon-aminocaproic acid 100 mg kg^–1before tourniquet deflation followed by continuous perfusion(1 g h^–1) during 3 h. External perioperative blood losswas measured and total blood loss was calculated. The numberof patients transfused and number of packed red cell (PRC) unitstransfused was recorded and possible postoperative thromboemboliccomplications were investigated. Results. Total blood loss [mean (SD)] was 1099 ml (535) in thegroup that received antifibrinolytic agents and 1784 ml (660)in the control group (P<0.001). Five patients (7.5%) in thestudy group and 23 (38.3%) in the control group (P<0.001)received blood transfusions; the first group received a meanof 0.10 PRC unit per patient and the second, 0.58 (P<0.001).Mean reduction in haemoglobin levels (g dl^–1) betweenpreoperative and fifth day postoperative readings was 2.5 (0.9)in the study group and 3.4 (1.2) in the control group (P<0.001).Clinical assessment did not reveal any thromboembolic complications. Conclusions. Antifibrinolytic agents produce a significant decreasein blood loss in patients undergoing total knee replacement,reflected in a reduction in the number of blood transfusionsrequired.     

Safety of oral nicorandil before coronary artery bypass graft surgery

Nicorandil is a K_ATP channel opener used to treat angina. Itis cardioprotective and a vasodilator. We conducted a prospective,randomized, double-blind, placebo-controlled study to assessoral nicorandil in patients undergoing coronary artery bypassgrafting (CABG) with cardiopulmonary bypass (CPB). Twenty-twopatients received nicorandil (10 mg twice a day) and 23patients received placebo. Haemodynamic data were recorded beforeinduction of anaesthesia (T0), 5 and 20 min after startingmechanical ventilation (T1, T2), before aortic cannulation (T3),after 30 min of CPB (T4), 10 min after CPB (T5) andafter 3, 8 and 18 h in the intensive care unit (T6, T7,T8). Serum proteins (creatine kinase metabolite and cardiactroponin I) were measured before and 8 and 18 h after surgery.Haemodynamic values did not differ between the two groups. Therewas no tachycardia during the study, no significant differencein hypotensive episodes, ST segment changes and no changes incardiac enzymes. Myocardial infarction after surgery was similarin the two groups. Vasoactive therapy was similar in the twogroups. Nicorandil can be continued safely up to premedicationwithout deleterious haemodynamic consequences, but a myocardialprotective effect of nicorandil in CABG surgery was not found. Br J Anaesth 2001; 87: 848–54     

Adding lactate to the prime solution during hypothermic cardiopulmonary bypass: a quantitative acid-base analysis

Background. The effect of adding lactate to the cardiopulmonarybypass (CPB) prime was investigated using Stewart’s quantitativeacid–base approach. According to this quantitative model,serum pH and bicarbonate are determined by three independentfactors: the partial pressure of carbon dioxide (PCO₂), thetotal concentration of weak acids (e.g. albumin), and the strongion difference. The apparent strong ion difference is calculatedas the sum of sodium, potassium, magnesium and calcium minuschloride concentrations. The pH decreases with a smaller strongion difference and vice versa. Methods. Twenty patients scheduled for coronary surgery werestudied prospectively. All patients were treated identically,except for the prime, which either contained lactate or waslactate free. Just before bypass and before coming off bypass,haemoglobin, glucose, plasma osmolality and colloid osmoticpressure were determined; albumin, lactate, sodium, potassium,ionized calcium, magnesium, phosphate, arterial pH, PCO₂, bicarbonate,and base excess were measured for use in Stewart’s analysis. Results. Metabolic acidosis had resolved by the end of bypasswith the lactated prime. Although the strong ion gap (apparentminus effective strong ion difference) increased significantlyin both groups, its composition differed significantly betweenthe groups. The Stewart technique detected polyanionic gelatinas a weak acid component contributing to the unidentified anionfraction. Colloid osmotic pressure was maintained in both groups. Conclusion. Exogenous lactate attenuates acidosis related toCPB. The oncotic and weak acid deficits produced by hypoalbuminaemiamay be compensated for temporarily during CPB by polyanionicsynthetic colloids such as succinylated gelatin. Br J Anaesth 2003; 90: 440–5     

Increased concentrations of L-lactate in the rectal lumen in patients undergoing cardiopulmonary bypass

Background. Gut ischaemia may contribute to morbidity in patientsafter cardiopulmonary bypass (CPB), but little is known aboutthe metabolic state of the large bowel in such patients. Thereforewe estimated the concentrations of L-lactate and in rectal mucosa in patients undergoing cardiac surgery withor without the use of CPB. Methods. Patients undergoing coronary artery bypass grafting(CABG) (n=12) or off-pump CABG (n=10) were subjected to equilibriumdialysis of the rectal lumen during the procedure and in thefirst 4 h afterwards. Dialysate concentrations of L-lactateand were measured using an auto-analyser and compared with values obtained in healthy subjects (n=10). Results. During CPB, a 2- to 3-fold increase in luminal concentrationsof L-lactate was observed (CABG vs off-pump CABG, P=0.05; CABGvs healthy subjects, P<0.01). The dialysate concentrationsof L-lactate were higher than the mean systemic values (luminal–arterialgradient mean (SD) 0.9 (1.0) mmol litre^–1, P<0.05),and the two values were positively correlated (P<0.05). LuminalL-lactate concentrations remained elevated 4 h after the operation.In contrast, dialysate was equally high in patient and control groups and substantially higher thanvalues observed in arterial blood. Conclusions. Uncomplicated CPB is associated with moderate butsustained increases in luminal concentrations of L-lactate inthe rectum, indicating metabolic dysfunction of the mucosa inthe large bowel. Part of this study was presented at the 27th Congress of theScandinavian Society of Anaesthesiology and Intensive Care Medicine,Helsinki, Finland, 2003.     

Effects of chronic angiotensin II receptor antagonist and angiotensin-converting enzyme inhibitor treatments on neurohormonal levels and haemodynamics during cardiopulmonary bypass

Background. Chronic treatment with renin-angiotensin system(RAS) antagonists frequently causes deleterious hypotensionduring anaesthesia. We compared the effects of angiotensin IIreceptor antagonists (ARA) and angiotensin-converting enzymeinhibitors (ACEI) on neurohormonal levels and haemodynamicsduring cardiopulmonary bypass (CPB). Methods. Forty-four patients undergoing mitral valvular surgerywho were treated with either ARA (ARA group, n=14) or ACEI (ACEIgroup, n=15) over 12 weeks or who were not treated with anyRAS antagonist (control group, n=15) were enrolled. The plasmalevels of epinephrine, norepinephrine, arginine vasopressin(AVP) and angiotensin II, and haemodynamic variables were measuredbefore (T1) and 15 min after (T2) the start of CPB, before aorticunclamping (T3) and at skin closure (T4). Mean arterial pressure(MAP) was maintained above 60 mm Hg with phenylephrine administrationduring CPB. Results. The plasma epinephrine, norepinephrine, AVP and angiotensinII levels increased during CPB in all groups. Compared withthe control group, the AVP level was lower at T1 in the ARAgroup and at T2 in the ARA and ACEI groups. The angiotensinII level was higher at T1, T2 and T3 in ARA group compared withACEI and control groups. There were no significant differencesin the epinephrine and norepinephrine levels among the threegroups. The amount of administered phenylephrine during CPBwas greater and MAP was lower in the ARA group compared withthe ACEI and control groups. Conclusions. Chronic ARA treatment resulted in more profoundhypotension than ACEI treatment during CPB, and this may beassociated with the blockade of angiotensin II receptors byARA.