Myocardial infarction and cerebrovascular accident following non-cardiac surgery: differences in postoperative temporal distribution and risk factors.

BACKGROUND: Myocardial infarction and stroke after non-cardiac surgery are two ominous cardiovascular complications believed to share similar pathophysiological processes. However, the differences in the temporal distribution between them have not been adequately investigated in a large cohort of patients. METHODS AND RESULTS: The preoperative clinical features and daily occurrence of myocardial infarction and stroke were routinely recorded in 36 634 consecutive patients following elective non-cardiac, non-carotid surgery. The preoperative characteristics and postoperative daily distribution of postoperative myocardial infarction and stroke were compared using exponential and linear regressions models. Myocardial infarction and stroke occurred in 122 (0.33%) and 126 (0.34%) patients, respectively, during the first 30 days after surgery. More patients with myocardial infarction had diabetes mellitus and cardiac disease (P = 0.041 and <0.0001, respectively) whereas more patients with stroke were older and female (P = 0.003 and 0.038, respectively). The peak incidence of myocardial infarction was on the day of surgery (43%) and declined exponentially thereafter (F = 725.4, P < 0.0001). However, postoperative stroke best fitted a linear regression with almost even daily distribution (F = 15.9, P = 0.0004). The median time to myocardial infarction was one day [95% confidence interval (95% CI) = 0-2 days] compared with nine days (95% CI = 7-11 days) for stroke. CONCLUSIONS: The peak incidence of postoperative myocardial infarction is early after non-cardiac surgery and declines exponentially thereafter, as opposed to stroke, which occurs at a constant rate during the postoperative period. Myocardial infarction and cerebrovascular accident following non-cardiac surgery differ in their preoperative risk factors, and in the postoperative time-line of their occurrence.

Age and comorbidity as risk factors for vocal cord paralysis associated with tracheal intubation.

BACKGROUND: Vocal cord paralysis after tracheal intubation may be attributed to ageing and comorbidity. However, the relationship between patient characteristics and the risk of vocal cord paralysis is unknown. METHODS: We prospectively analysed data representing 31 241 consecutive surgery patients who underwent tracheal intubation to determine whether duration of intubation, age, sex, and cardiovascular, cerebrovascular, and metabolic diseases were risk factors for vocal cord paralysis associated with intubation. Patients with vocal cord paralysis from any other causes were excluded. RESULTS: Twenty-four (0.077%) suffered vocal cord paralysis (left, 16 patients; right, 8 patients). The risk was increased when intubation lasted 3-6 h (odds ratio, 2.0; 95% confidence interval, 1.1-5.6; P = 0.002) or 6 h or more (odds ratio, 14.5; 95% confidence interval, 5.2-40.9; P < 0.0001). The risk was increased in patients aged 50-69 (odds ratio, 3.6; 95% confidence interval, 1.2-11.1; P = 0.02) and 70 yr or above (odds ratio, 3.9; 95% confidence interval, 1.2-12.8; P = 0.02). The risk was increased with diabetes mellitus (odds ratio, 2.5; 95% confidence interval, 1.1-7.3; P = 0.03) and hypertension (odds ratio, 2.1; 95% confidence interval, 1.1-6.0; P = 0.03). CONCLUSIONS: The risk of vocal cord paralysis was increased three-fold in patients aged 50 or above, two-fold in patients intubated 3-6 h, 15-fold in patients intubated 6 h or more, and two-fold in patients with a history of diabetes mellitus or hypertension. Our results are informative for informed consent, patient counselling, and intubation decision-making.

Relation between initial blood distribution volume and propofol induction dose requirement.

BACKGROUND: Propofol induction dose is variable and depends on many factors, including initial volume of distribution and early disposition. The authors hypothesized that preadministration blood distribution volumes, cardiac output (CO), and hepatic blood flow (HBF) could be examined to establish a propofol induction dose. METHODS: Propofol dose required to reach loss of consciousness, when infused at infusion rate per lean body mass (LBM) of 40 mg x kg(-1) x h(-1), was determined in 75 patients aged 11-85 yr. CO, blood volume (BV), central blood volume (CBV), and HBF were measured with indocyanine green pulse spectrophotometry. Univariate least squares linear regression analysis was used to individually analyze the relation between propofol induction dose and patient characteristics, including LBM, baseline distribution volumes, CO, and HBF. Stepwise multiple linear regression models were used to select important predictors of induction dose. RESULTS: Although there was a significant correlation between the induction dose and each of the eight variables of age, sex, LBM, hemoglobin, CO, BV, CBV, and HBF, only factors of age (partial r = -0.655), LBM (partial r = 0.325), CBV (partial r = 0.540), and HBF (partial r = 0.357) were independently associated with the induction dose (R2 = 0.85) when all variables were included in a multivariate model. CONCLUSIONS: At a constant propofol infusion rate of 40 mg x kg(-1) x h(-1) as a function of LBM in patients with American Society of Anesthesiologists physical status I or II, the induction dose can be determined from four variables: age, LBM, CBV, and HBF.

Optimal propofol plasma concentration during upper gastrointestinal endoscopy in young, middle-aged, and elderly patients.

BACKGROUND: Suitable propofol plasma concentrations during gastroscopy have not been determined for suppressing somatic and hemodynamic responses in different age groups. METHODS: Propofol sedation at target plasma concentrations from 0.5 to 4.0 microgram/ml were performed randomly in three groups of patients (23 per group) who were undergoing elective outpatient gastroscopy: ages 17-49 yr (group 1), 50-69 yr (group 2), and 70-89 yr (group 3). Plasma propofol concentration in which 50% of patients do not respond to these different stimuli were determined by logistic regression: verbal command (Cp50ls), somatic response to gastroscopy (Cp50endo), and gag response to gastroscopy (Cp50gag). Hemodynamic responses were also investigated in the different age groups. RESULTS: Cp50ls concentrations were 2.23 microgram/ml (group 1), 1.75 microgram/ml (group 2), and 1.40 microgram/ml (group 3). The Cp50endo values in groups 1 and 2 were 2.87 and 2.34 microgram/ml, respectively, which were significantly higher than their respective Cp50ls values. Cp50endo value in group 3 was 1.64 microgram/ml, which was close to its Cp50ls value. Because of a high degree of interpatient variability, Cp50gag could not be defined. Systolic blood pressure response decreased with increasing propofol concentrations. CONCLUSIONS: The authors determined the propofol concentration necessary for gastroscopy and showed that increasing age reduces it. Propofol concentration that suppresses somatic response induces loss of consciousness in almost all young patients.

Investigation of effective anesthesia induction doses using a wide range of infusion rates with undiluted and diluted propofol.

BACKGROUND: The influence of infusion rate on the induction dose-response relation has not been investigated over a wide range of infusion rates. In this study, the authors defined the effect of different propofol infusion rates on the times and doses necessary to reach clinical induction of anesthesia. METHODS: The subjects of the study were 250 patients classified as American Society of Anesthesiologists physical status I or II aged 25-55 yr. For induction with undiluted propofol, 180 patients were allocated randomly to one of two groups of 90 patients each (A and B). Each group was further divided into nine subgroups (10 patients each) that were administered propofol infusion at rates of 10, 15, 20, 30, 40, 60, 100, 200, and 300 mg/kg-1/h-1. The remaining 70 patients (group C) were allocated randomly into seven subgroups (10 patients each), and these groups were induced with diluted propofol (0.5 mg/ ml) at the rates of 10, 15, 30, 60, 100, 200, and 300 mg/kg-1/ h-1. Group B was given crystalloid at the same infusion rates as group C via a catheter in the opposite arm. Induction time, induction dose, plasma arterial propofol concentration at loss of consciousness, and percentage decrease of systolic blood pressure were measured. A previously reported three-compartment model with an effect-site rate constant for propofol of 0.456/min was used to predict the induction time and dose at each infusion rate. RESULTS: The differences between predicted induction time and dose and the observed time and dose could be explained by factoring in the lag time from infusion site to central compartment (lag time circulation) and the amount of propofol in transit during this time (residual dose circulation). Residual dose circulation and lag time circulation correlated with infusion time from 20 to 60 s for undiluted and from 0 to 40 s for diluted propofol. At the infusion rates greater than 80 mg/kg-1/h-1, rapid circulation because of incomplete mixing in the central compartment decreased the excess induction time and dose. The use of diluted propofol significantly attenuated the decrease in systolic blood pressure provoked by the residual dose circulation. CONCLUSIONS: Induction dose and time are dependent on infusion rate in a complex manner, and residual dose circulation was a factor in overdose and hemodynamic depression. Hypotension during induction was attenuated by diluted propofol.

Treatment of intractable diseased tissue in the maxillary sinus after endoscopic sinus surgery with high-pressure water jet and preservation of the periosteum.

OBJECTIVE: To describe a new high-pressure water jet (HPWJ) treatment to remove intractable diseased mucosa persisting in the maxillary sinus several months after endoscopic sinus surgery (ESS) while preserving the periosteum. DESIGN: A retrospective review of HPWJ treatment in 45 consecutive patients with at least 12 months follow-up. SETTING: A private surgicenter in Japan. PATIENTS: Patients (25 male and 20 female) ranged in age from 8 to 59 years. All patients had diffuse intractable lesions in the opened maxillary sinus after the initial ESS, with or without disease of the ethmoid and other major sinuses. MAIN OUTCOME MEASURES: Resolution of diffuse intractable disease in the maxillary sinus and postoperative change in the size of the cavity were evaluated using nasal endoscopy and computed tomographic scan. RESULTS: Twenty-six (81%) of 32 sides in 25 patients with isolated persistent maxillary sinus disease were restored after HPWJ procedures; 25 (93%) of 27 sides in 20 patients who also had ethmoiditis also were restored. In the latter group, ethmoiditis recurred in 5 sides, which also included 2 sides of unrestored maxillary sinuses. Of the 51 restored sides, 33 (65%) were restored within 3 months after HPWJ treatment under endoscopic observation. No complications were seen during the surgery. Except for 1 side in 1 patient from which all diseased mucosa was removed almost completely, along with the periosteum, no reduction of the cavity by scar tissue formation was observed. This method did not affect the development of the maxillary bone in children. CONCLUSION: Removing diffuse intractable diseased mucosa in the maxillary sinus while preserving the periosteum with HPWJ treatment is an effective surgical therapy that fulfills the ultimate purpose of ESS.

Disaggregatory effects of prostaglandin E1, amrinone and milrinone on platelet aggregation in human whole blood.

Prostaglandin E1 (PGE1), amrinone and milrinone not only inhibit platelet aggregation, but also potentially induce disaggregation. We examined the disaggregatory effects of PGE1, amrinone and milrinone on platelet aggregation, and measured the platelet cyclic adenosine monophosphate (cAMP) levels using a standard radioimmunoassay. Platelet aggregation was induced by 10 microM adenosine diphosphate (ADP) or 0.625 microg/ml collagen that induces a secondary aggregation, and measured by whole blood aggregometry. PGE1 (0.7-10.0 microM), amrinone (106.8-801.3 microM), or milrinone (9.5-190.0 microM) was added when aggregation reached 5 mohm of impedance, and the percentage of disaggregation was measured 5 min after initiating disaggregation. Disaggregatory effects were also examined using a light transmission aggregometer and gel-filtered platelets. In platelet aggregation induced by ADP, the drug concentrations required to cause 50% disaggregation (EC50) were PGE1; 3.1+/-1.2 microM, amrinone; 313.1+/-128.8 microM, milrinone; 57.1+/-20.8 microM. In platelet aggregation induced by collagen, the maximum disaggregation percentages were 15.6+/-5.0% for 10 microM PGE1, 7.8+/-2.4% for 801.3 microM amrinone, and 5.9+/-2.3% for 190.0 microM milrinone. The EC50 concentrations of platelet cAMP that caused 50% disaggregation in ADP-induced platelet aggregation were 67+/-13 pmoles/10(8) platelets for PGE1, 54+/-12 pmoles/10(8) platelets for amrinone, and 52+/-12 pmoles/10(8) platelets for milrinone. In gel-filtered platelets, the percentages of disaggregation in ADP- or collagen-induced platelet aggregation were 33.1+/-5.2% or 11.2+/-3.1% for PGE1 (10 microM), 22.3+/-4.1% or 15.2+/-3.2% for amrinone (801.3 microM), and 23.5+/-4.3% or 14.6+/-3.5% for milrinone (190.0 microM).

Comparison of the effect-site k(eO)s of propofol for blood pressure and EEG bispectral index in elderly and younger patients.

BACKGROUND: Drug effect lags behind the blood concentration. The goal of this investigation was to determine the time course of plasma concentration and the effects of propofol demonstrated by electroencephalogram or blood pressure changes and to compare them between elderly and young or middle-aged patients. METHODS: A target-controlled infusion was used to rapidly attain and maintain four sequentially increasing, randomly selected plasma propofol concentrations from 1 to 12 microg/ml in 41 patients aged 20-85 yr. The target concentration was maintained for about 30 min. Bispectral index (BIS), spectral edge frequency, and systolic blood pressure (SBP) were used as measures of propofol effect. Because the time courses of these measures following the started drug infusion showed an exponential pattern, the first-order rate constant for equilibration of the effect site with the plasma concentration (k(eO)) was estimated by fitting a monoexponential model to the effect versus time data resulting from the pseudo-steady-state propofol plasma concentration profile. RESULTS: The half-times for the plasma-effect-site equilibration for BIS were 2.31, 2.30, 2.29, and 2.37 min in patients aged 20-39, 40-59, 60-69, and 70-85 yr, respectively (n = 10 or 11 each). The half-times for SBP were 5.68, 5.92, 8.87, and 10.22 min in the respective age groups. All were significantly longer than for BIS (P < 0.05). The propofol concentration at half of the maximal decrease of SBP was significantly greater (P < 0.05) in the elderly than in the younger patients. CONCLUSIONS: The effect of propofol on BIS occurs more rapidly than its effect on SBP. Age has no effect on the rate of BIS reduction with increasing propofol concentration, whereas with increasing age, SBP decreases to a greater degree but more slowly.

Less core hypothermia when anesthesia is induced with inhaled sevoflurane than with intravenous propofol.

UNLABELLED: Hypothermia after the induction of anesthesia results initially from core-to-peripheral redistribution of body heat. Sevoflurane and propofol both inhibit central thermoregulatory control, thus causing vasodilation. Propofol differs from sevoflurane in producing substantial peripheral vasodilation. This vasodilation is likely to facilitate core-to-peripheral redistribution of heat. Once heat is dissipated from the core, it cannot be recovered. We therefore tested the hypothesis that the induction of anesthesia with i.v. propofol causes more core hypothermia than induction with inhaled sevoflurane. We studied patients undergoing minor oral surgery randomly assigned to anesthetic induction with either 2.5 mg/kg propofol (n = 10) or inhalation of 5% sevoflurane (n = 10). Anesthesia in both groups was subsequently maintained with sevoflurane and 60% nitrous oxide in oxygen. Calf minus toe skin temperature gradients <0 degrees C were considered indicative of significant vasodilation. Ambient temperature and end-tidal concentrations of maintenance sevoflurane were comparable in each group. Patients in both groups were vasodilated throughout most of the surgery. Nonetheless, core temperatures in patients who received propofol were significantly lower than those in patients who received inhaled sevoflurane. These data support our hypothesis that even a brief period of vasodilation causes substantial redistribution hypothermia that persists throughout surgery. IMPLICATIONS: Core temperatures in patients who received i.v. propofol were consistently lower than those in patients who received inhaled sevoflurane, although anesthesia was subsequently maintained with sevoflurane in nitrous oxide in both groups. This suggests that even a brief period of propofol-induced vasodilation during anesthetic induction causes substantial redistribution hypothermia that persists throughout surgery.

Extended endoscopic frontal sinus surgery to interrupted nasofrontal communication caused by scarring of the anterior ethmoid: long-term results.

OBJECTIVE: To examine the long-term results of extended endoscopic frontal sinus surgery, including removal of the floor of the frontal sinus (Draf type II procedure) and the median drainage operation (Draf type III procedure or modified Lothrop procedure), for obstructive frontal sinusitis caused by postoperative scar formation, with the emphasis on the long-term success of the median drainage procedure. DESIGN: Retrospective review of 22 consecutive cases of extended endonasal frontal sinus surgery in patients with obstructive frontal sinusitis caused by postoperative scarring. SETTING: The procedures were performed at a private surgicenter in Japan. PATIENTS: Twenty-two patients (15 males and 7 females) ranging in age from 14 to 61 years. All patients had scar formation in the anterior ethmoid, either with or without middle turbinate lateralization or ethmoiditis. Three patients underwent Draf type II procedure followed by Draf type III procedure because of surgical failure of the type II procedure. MAIN OUTCOME MEASURES: Restoration of communication to the frontal sinus was evaluated by computed tomography. All patients were examined at least 12 months after surgery or stent removal. RESULTS: Of the 16 patients who underwent the type III procedure, in 14 (88%) the patency of the opening to the frontal sinus and an aerated sinus were confirmed. Of 12 sides in 9 patients who underwent Draf type III procedure, 5 sides (42%) were also confirmed as "cured." CONCLUSIONS: The median drainage operation (Draf type III procedure) on the frontal sinus showed excellent long-term results compared with the type II procedure. Extended endoscopic frontal sinus surgery, particularly the median drainage procedure, is useful in the functional treatment of obstructive frontal sinusitis caused by postoperative scarring.

Lithium dilution cardiac output measurements using a peripheral injection site comparison with central injection technique and thermodilution.

OBJECTIVE: The lithium dilution technique for the measurement of cardiac output by the central injection of lithium chloride was introduced by Linton et al. in 1993. In the present report, we compare lithium dilution cardiac output measurement (LD) by the peripheral injection of lithium chloride (pLD) and by central venous injection (cLD), cardiac output determined by electromagnetic flowmetry (EM), and conventional thermodilution cardiac output measurement (TD) on ten swine. METHODS: The animals were monitored with a pulmonary artery catheter, a femoral artery catheter, and an electromagnetic flowmeter placed around the ascending aorta. cLD, pLD, TD, and EM were determined at the baseline, then in a hyperdynamic state produced by dobutamine administration, at a second baseline, and finally in a hypodynamic state induced by propranolol during deep anesthesia. Data were analyzed by linear regression analysis and the comparison method described by Bland and Altman; bias and precision were calculated using the method of Sheiner and Beal. RESULTS: The correlation coefficient between pLD and EM (0.86) was significantly less than that between cLD and EM (0.96), however it was not significantly different from that between TD and EM (0.85). The precision value of pLD (0.14) was the same as that of TD (0.14). CONCLUSION: The results of the present study indicate that pLD is a reliable technique.

A bolus dose of 1.5 mg/kg amrinone effectively improves low cardiac output state following separation from cardiopulmonary bypass in cardiac surgical patients.

BACKGROUND: The aim of this study was to evaluate the efficacy of 1.5 mg/kg bolus of amrinone on low cardiac output (CO) state following emergence from cardiopulmonary bypass (CPB) in cardiac surgical patients. METHODS: Immediately after emergency from CPB, 14 patients with a cardiac index (CI) less than 2.2 l.min-1.m-2 despite administration of inotropes and nitroglycerin, received 1.5 mg/kg amrinone over 3 min without changing catecholamine infusion rates (amrinone group). Hemodynamics and left ventricular short axis views with transesophageal echocardiography were recorded at baseline, 3, 4, and 10 min following amrinone administration. Left ventricular filling volumes were maintained constant by volume reinfusion from the CPB reservoir. We matched the data of the amrinone group with the other 14 patients who did not receive amrinone (non-amrinone group) to evaluate the efficacy of amrinone in low CO state. RESULTS: At baseline, CI (1.8 +/- 0.1 l.min-1.m-2) in the amrinone group was significantly lower than CI (3.0 +/- 0.2) in the non-amrinone group. Following amrinone administration, CI and velocity of circumferential fibershortening corrected for heart rate (Vcfc) significantly increased, and systemic vascular resistance index and pulmonary vascular resistance index significantly decreased from the baseline within 10 min without changes in heart rate, mean arterial blood pressure, or pulmonary artery occlusion pressure, and became equivalent with those of the non-amrinone group. CONCLUSIONS: A 1.5 mg/kg amrinone loading dose to patients in a low CO state, despite catecholamine therapy immediately after emergence from CPB, effectively improves ventricular function when loading conditions are maintained constant.

Propofol concentration required for endotracheal intubation with a laryngoscope or fiberscope and its interaction with fentanyl.

UNLABELLED: The administration of fentanyl with propofol reduces the blood concentration of propofol required to achieve adequate anesthesia for tracheal intubation. However, different intubation procedures have variable intensities of noxious stimulation and may require different levels of anesthesia. The goal of this study was to determine the propofol blood concentration at which 50% of patients did not respond to stimulation (Cp50) for laryngoscopy, intubation with a laryngoscope, insertion of a slotted oral-pharyngeal airway (Ovassapian airway), and intubation with a fiberscope when administered in conjunction with fentanyl. Patients undergoing elective surgery were given varying amounts of propofol or propofol with fentanyl, and their responses to the four procedures listed above were assessed. These experiments demonstrated that the propofol concentration required for intubation with a laryngoscope was similar to that for intubation with a fiberscope, and that the required level was reduced by fentanyl. Hemodynamic responses to intubation were lower with a fiberscope than with a laryngoscope. We conclude that almost the same concentrations of propofol or fentanyl are necessary for suppressing both of the somatic responses to tracheal intubation with a fiberscope or a laryngoscope. Hemodynamic responses were attenuated more during intubation with a fiberscope. IMPLICATIONS: The propofol blood concentrations at which 50% of patients did not respond to stimulation for laryngoscopy, tracheal intubation with a laryngoscope, and tracheal intubation with a fiberscope were 10.9, 19.6, and 19.9 microg/mL, respectively. These were reduced by fentanyl. Hemodynamic responses to intubation were less with a fiberscope than with a laryngoscope.

The effect of milrinone on hemodynamics and left ventricular function after emergence from cardiopulmonary bypass.

Although milrinone effectively increases cardiac function, few studies have specifically evaluated its efficacy during cardiac surgery. We investigated the effects of milrinone on hemodynamics and left ventricular function in cardiac surgical patients who were already treated with catecholamines. Thirty-seven patients undergoing cardiac surgery were studied. Immediately after emergence from cardiopulmonary bypass (CPB), patients were randomly assigned to a control group (n = 10) or to one of these milrinone groups: milrinone 50 microg/kg intravenously (n = 8), 50 microg/kg + 0.5 microg x kg(-1) x min(-1) (n = 10), or 75 microg/kg + 0.75 microg x kg(-1) x min(-1) (n = 9). Hemodynamics and transesophageal echocardiogram were recorded while constant filling pressures were maintained by volume reinfusion from the CPB reservoir. Arterial blood samples were obtained for the measurement of milrinone plasma concentrations and to determine the dose response curve. In all three milrinone groups, cardiac index and velocity of circumferential fiber shortening (Vcfc) significantly increased from the baseline, and both were significantly higher at 5 and 10 min than those in the control group. The plasma concentration of milrinone with half of maximum increase in Vcfc was 139.3 ng/mL based on the dose-response curve. Thus, milrinone improves hemodynamics and left ventricular function when constant loading conditions are maintained.

Assessment of a new ventricular contractile index obtained with transoesophageal echocardiography before and after cardiopulmonary bypass in cardiac surgical patients.

We have compared a new contractile index "left ventricular end-systolic wall stress-heart rate-corrected velocity of circumferential fibre shortening (vcfc)" with conventional contractile indices in 13 patients undergoing coronary artery bypass grafting. We generated the slopes of the "end-systolic wall stress-vcfc", "end-systolic wall stress-area" and "peak arterial pressure-area" relationships by altering arterial pressure before and after cardiopulmonary bypass (CPB). In all patients, significant correlations were obtained for end-systolic wall stress-area and peak arterial pressure-area relationships before and after CPB. In all patients, significant inverse linear correlations were obtained for the end-systolic wall stress-vcfc relationship before CPB; however, inverse linear correlation was absent in eight patients after CPB. It may be that the increased afterload had less influence on left ventricular systolic function after CPB as a possible mechanism of loss of the inverse linear correlation in the end-systolic wall stress-vcfc relationship.

Comparison of the accuracy of the lithium dilution technique with the thermodilution technique for measurement of cardiac output.

A new indicator dilution technique for measurement of cardiac output is described. Lithium chloride is injected via a central venous catheter and its dilution curve measured in arterial blood using a lithium-selective electrode. We assessed the lithium dilution cardiac output measurement (LiDCO) and a conventional thermodilution cardiac output measurement (ThDCO) by comparing the results of both with cardiac output determined by electromagnetic flowmetry (EMCO) under controlled laboratory conditions in 10 swine. They were monitored with a pulmonary artery catheter, femoral artery catheter and electromagnetic flowmeter placed around the ascending aorta. LiDCO, ThDCO and EMCO measurements were determined at baseline, in a hyperdynamic state produced by administration of dobutamine, at a second baseline and finally in a hypodynamic state induced by propranolol during deep anaesthesia. Data were analysed by linear regression analysis and the comparison method described by Bland and Altman; bias and precision of both LiDCO and ThDCO compared with EMCO were calculated by the method of Sheiner and Beal. The correlation coefficient between LiDCO and EMCO (0.95) was higher than that between ThDCO and EMCO (0.87). The precision value of LiDCO (0.04) was significantly less (i.e. better) than that of ThDCO (0.09). The results of this study indicated that LiDCO was more reliable compared with conventional ThDCO.

Heparinase I (neutralase) reversal of systemic anticoagulation.

BACKGROUND: Protamine causes multiple adverse reactions. Heparinase I, a specific enzyme that inactivates heparin, is a possible alternative to protamine. In this study, the authors examined the efficacy of heparinase I to reverse heparin-induced anticoagulation in vitro and compared heparinase I to protamine as an antagonist of heparin-induced anticoagulation in dogs. METHODS: In the in vitro study, blood was obtained from the extracorporeal circuits of 12 patients, and activated clotting times were determined after adding different concentrations of heparinase I. In the in vivo study, 24 anesthetized dogs received 300 units/kg heparin injected intravenously for 5 s, then 10 min later, 3.9 mg/kg protamine, 5-41 micrograms/kg heparinase I, or the vehicle (n = 4/group) were administered intravenously, and activated clotting times and hemodynamics were measured. RESULTS: In the in vitro study, heparin concentrations of 3.3 +/- 1.0 (mean +/- SD) units/ml (approximately 0.033 mg/ml; n = 12) were reversed in the blood of patients by heparinase I at concentrations > 0.490 microgram/ml. In the canine study, heparinase at all doses studied and protamine effectively reversed the anticoagulating effects of heparin within 10 min of administration. Protamine produced adverse hemodynamic effects, whereas heparinase or its vehicle produced no significant change in arterial pressure. CONCLUSION: Both heparinase I and protamine effectively reversed heparin anticoagulation. However, as opposed to protamine, heparinase I did not produce any significant hemodynamic changes when given as a bolus to dogs.

Heparin neutralization with methylene blue, hexadimethrine, or vancomycin after cardiopulmonary bypass.

There are no clinically available alternatives for reversing heparin in protamine-allergic patients. This study examined the ability of methylene blue, hexadimethrine, and vancomycin to reverse circulating heparin so that these compounds can be carefully examined in future placebo-controlled studies in humans. Heparin activity in blood obtained from extracorporeal circuits was reversed by adding protamine (13.5, 27.0, 81.1, 135.1, and 270.3 micrograms/mL), methylene blue (13.5, 27.0, 135.1, 202.7, 270.3, 337.8, 405.4, 473.0, 540.5, and 810.8 micrograms/mL), hexadimethrine (6.8, 13.5, 20.3, 27.0, 81.1, and 135.1 micrograms/mL), or vancomycin (13.5, 27.0, 135.1, 270.3, 540.5, and 810.8 micrograms/mL), and activated clotting times (ACTs) were measured with kaolin (n = 18). Heparinase-ACT was obtained to determine complete reversal. Heparin concentrations were 3.3 +/- 0.3 U/mL with ACT values of 485 +/- 97 s. The ACT at a protamine concentration of 81.1 micrograms/mL and at hexadimethrine concentrations of 81.1 and 135.1 micrograms/mL was not statistically different from heparinase-ACT; however, methylene blue or vancomycin did not reverse the anticoagulation at any concentrations. Hexadimethrine can reverse heparin-induced anticoagulation after cardiopulmonary bypass as well as protamine, although methylene blue or vancomycin did not neutralize heparin in vitro.

Carbon dioxide output in laparoscopic cholecystectomy.

In pneumoperitoneum, carbon dioxide eliminated in expired gas (carbon dioxide output) contains both metabolic and absorbed carbon dioxide from the peritoneal cavity. When elimination of carbon dioxide is much higher than carbon dioxide output, storage of tissue carbon dioxide and arterial carbon dioxide concentrations change. Finally, the rate of carbon dioxide eliminated in expired gas is not a match for the real rate of metabolic production and absorbed carbon dioxide from the peritoneal cavity. During and after insufflation of carbon dioxide, changes in carbon dioxide output were elucidated under constant arterial carbon dioxide pressure (PaCO2), the same as the preinduction level. We studied patients undergoing elective laparoscopic cholecystectomy. Carbon dioxide output, oxygen uptake, respiratory exchange ratio (RER), expired minute ventilation (VE), deadspace to tidal volume ratio (VD/VT ratio) and arterial to end-tidal carbon dioxide partial pressure difference (PaCO2-PE'CO2) were determined before induction, and during anaesthesia, pneumoperitoneum and recovery. By controlling ventilatory frequency (f) every 1 min, PaCO2 was adjusted to concentrations before induction. Constant monitoring of end-tidal carbon dioxide partial pressure (PE'CO2) and intermittent measurement of (PaCO2-PE'CO2) (15-min intervals) were conducted to predict PaCO2). Carbon dioxide output and oxygen uptake decreased significantly from mean values of 83.5 (SEM 5.2), 101.6 (5.1) to 68.5 (4.2), 81.1 (4.6) ml min-1 m-2 (ATPS, P < 0.05) with sevoflurane anaesthesia, and RER did not change. During carbon dioxide pneumoperitoneum (intra-abdominal pressure 8 mm Hg), carbon dioxide output increased by 49% (102.4 (5.0) ml min-1 m-2) (P < 0.05) while oxygen uptake remained stable and RER increased from 0.84 (0.02) to 1.16 (0.03) (P < 0.05). It was necessary to increase VE during pneumoperitoneum by 1.54 times that during anaesthesia to maintain individual PaCO2 values constant. After removal of carbon dioxide from the abdominal cavity, the regression equation of excess carbon dioxide output/BSA best fitted a two-compartment model. The time constants of the rapid and slow compartments were 8.2 and 990 min, respectively. Excess carbon dioxide output/BSA was still 5.5 ml min-1 m-2, 30 min after pneumoperitoneum.