Anaphylactoid reactions after cisatracurium administration in six patients.

IMPLICATIONS: We report six cases of anaphylactoid reaction after the administration of the muscle relaxant cisatracurium. They include two first-time documented anaphylactoid reactions after a precurarising dose. These incidents challenge existing views of a substantially reduced anaphylactoid potential of cisatracurium relative to other muscle relaxants.

Pseudocholinesterase-activity reduction during cardiopulmonary bypass: the role of dilutional processes and pharmacological agents.

UNLABELLED: 1. Pseudocholinesterase (ChE) activity is a determinant of the elimination kinetics of several drugs used in anesthesia. The time course of ChE activity was investigated in 16 patients undergoing cardiosurgery for a cardiopulmonary bypass (CPB) in normothermia or hypothermia. 2. The onset of the CPB was accompanied by a decrease in ChE activity (-37%) (P<0.05) and protein concentration (-24%) (P<0.05). The quotient ChE activity/protein concentration was numerically reduced to a smaller extent (-15%) (P>0.05). After the CPB was finished, ChE activity and the protein concentration remained low for the remaining operation time. 3. There was no difference in ChE activity, measured in vitro at 37 degrees C, between the normothermic and hypothermic group (P>0.05). 4. There was no correlation between heparin concentration in serum and reduction of ChE activity in vitro (P>0.05). In vitro, the ChE activity was not affected by either heparin in doses as high as 10,000 U/ml or aprotinin in doses as high as 10,000 U/ml (P>0.05). 5. CONCLUSIONS: (1) ChE activity is reduced by CPB mainly by hemodilution and (2) the pharmacological agents used in the present anesthetic technique (heparin, aprotinin, midazolam, fentanyl, propofol and mivacurium) do not inhibit ChE activity at therapeutic serum concentrations.

Lactated Ringer's solution versus hydroxyethyl starch for volume replacement in autologous blood donors with cardiovascular disease: a controlled, randomized trial.

BACKGROUND AND OBJECTIVES: The study was designed to evaluate whether volume replacement following blood donation can prevent arterial hypotension in autologous blood donors with cardiovascular disease. MATERIALS AND METHODS: One hundred nineteen autologous blood donors with known cardiovascular disease were randomly allocated to receive, following withdrawal of 500 ml of blood, either no infusion (control group) or a 25 ml/min intravenous infusion of either 1,500 ml of lactated Ringer's solution (LRS) or 500 ml of 6% hydroxyethyl starch (HES). Starting before phlebotomy, arterial blood pressure was measured oscillometrically every 5 min until 90 min after donation. RESULTS: Group means showed little difference between the groups in blood pressure throughout the monitoring period. The proportion of patients who at least once had a > or = 20% decrease from baseline in systolic blood pressure was 3-5 times greater in the control group than in the LRS and the HES group (50 vs. 10 and 15%, respectively; p < 0.001 on chi 2 analysis for a 2 x 3 table). Systolic hypertensive episodes (> or = 20% increase over baseline) were observed more frequently in the LRS group than in the control and the HES group (41 vs. 10 and 18%, respectively; p = 0.003). CONCLUSION: Both LRS and HES, administered at a volume ratio to blood loss of 3:1 and 1:1, respectively, significantly reduced the incidence of systolic hypotensive episodes in autologous blood donors with cardiovascular disease. LRS at a 3:1 volume ratio to blood loss was associated with a high rate of systolic hypertension.

The effects of increased doses of bovine hemoglobin on hemodynamics and oxygen transport in patients undergoing preoperative hemodilution for elective abdominal aortic surgery.

UNLABELLED: In two consecutive studies (Study A and Study B), we evaluated the effects of increasing doses of HBOC-201, a bovine hemoglobin-based oxygen carrier, on hemodynamics and oxygen transport in patients undergoing preoperative hemodilution for elective abdominal aortic surgery. After the induction of anesthesia and the exchange of 1 L of blood for 1 L of lactated Ringer's solution, 24 patients (12 in each study) were randomly assigned to receive, within 30 min, a predetermined volume of either HBOC-201 or 6% hydroxyethyl starch (Study A 6.9 mL/kg; Study B 9.2 mL/kg). Monitored variables included systemic and pulmonary arterial pressures, arterial and mixed venous blood gases, and calculations of cardiac index (CI), systemic (SVRI) and pulmonary (PVRI) vascular resistance indices, oxygen delivery index (DO2I), oxygen consumption index (VO2I), and oxygen extraction ratio (O2ER). In both studies, the infusion of HBOC-201 was associated with increases in SVRI (Study A 121%; Study B 71%) and PVRI (Study A 70%; Study B 53%) and with a decrease in CI (29% both studies). Hemodilution with HBOC-201 maintained the arterial oxygen content at levels higher than hemodilution with hydroxyethyl starch, but the advantage of a greater oxygen-carrying capacity was offset by the increase in SVRI, with a resulting net decrease in both CI and DO2I (Study A 30%; Study B 28%); VO2I was maintained by increased O2ER. In terms of hemodynamics and oxygen transport, hemodilution with bovine hemoglobin in these doses provided no apparent benefit over hemodilution with hydroxyethyl starch. IMPLICATIONS: Bovine hemoglobin in doses ranging between 55 and 97 g of hemoglobin increased vascular resistance and decreased cardiac output in anesthetized surgical patients. In terms of hemodynamics and oxygen transport, hemodilution with bovine hemoglobin in these doses provided no apparent benefit over hemodilution with hydroxyethyl starch.

All adverse events in autologous blood donors with cardiac disease are not necessarily caused by blood donation.

BACKGROUND: Autologous blood donation before elective cardiac surgery has become a standard of care at many institutions. However, the safety of autologous blood donations by patients with cardiac disease is subject to controversy. CASE REPORTS: Two life-threatening cardiac arrests and one fatal myocardial infarction that occurred in three patients who were scheduled to donate blood for autologous use in elective cardiac surgery are reported. All three patients met the institution's selection criteria for autologous blood donors, and all of them had given written informed consent for their participation in the autologous blood donation program. One of the two cardiac arrests and the myocardial infarction occurred in the patients prior to any blood donations, and the other cardiac arrest occurred 7 days after the patient donated blood uneventfully. CONCLUSION: Life-threatening and fatal adverse events may occur during the donation period in autologous blood donors with cardiac disease. Not all adverse events are necessarily caused by blood donation.

Preoperative red cell production in patients undergoing weekly autologous blood donation.

BACKGROUND: Modest autologous blood donation programs involving weekly phlebotomy and threshold hematocrits for blood donation higher than 33 percent are frequently used in patients scheduled for elective cardiac surgery. This study was performed to determine the gain in red cells (RBCs) obtained with such a program. STUDY DESIGN AND METHODS: The blood bank and medical records of 225 adult patients (194 men, 31 women; mean age, 57 years [range, 18-77]) who donated blood for autologous use in elective cardiac surgery during a 3-year period were reviewed. Preoperative RBC production was estimated by the total volume of RBCs donated minus the change in circulating RBC volume between the first donation and the day before surgery. RESULTS: A total of 604 blood units were donated (2.7 units/patient; range, 1-3). The mean volume of RBCs donated was 522 mL (range, 171-732). Mean RBC production (over baseline RBC production) was 351 mL (range, 9-719), or 19 percent (range, 0.5-40) of the circulating RBC volume at baseline. CONCLUSION: A modest autologous blood donation program using three phlebotomies at weekly intervals and a threshold hematocrit for blood donation of 36 percent yields an average of 351 mL (range, 9-719) of RBCs. This is equivalent to 2 units (range, 0.5-4) of allogeneic packed RBCs at 180 mL per unit.

A pilot study of continuous ambulatory electrocardiography in patients donating blood for autologous use in elective coronary artery bypass grafting.

BACKGROUND: A pilot study was conducted to evaluate the impact of a single autologous blood donation on the presence or absence of myocardial ischemic episodes in patients with coronary artery disease. STUDY DESIGN AND METHODS: Fifty patients scheduled for elective coronary artery bypass grafting underwent two 24-hour periods of ambulatory electrocardiogram monitoring, one before and one after their first autologous blood donation. The presence or absence and the number, duration, and integral area of episodes of ST segment depression for each 24-hour monitoring period were determined. RESULTS: Forty-two patients had legible electrocardiogram recordings for both monitoring periods. Of these, 36 patients (86%) had at least one episode of ST segment depression during any monitoring period. The number of patients who had at least one episode of ST segment depression before donation was not significantly different from the number of those who had at least one episode after donation (31 and 33 patients, respectively; p = 0.73). CONCLUSION: Donating a unit of blood had no demonstrable effect on the presence or absence of myocardial ischemic episodes in this sample of 42 autologous blood donors with coronary artery disease. The results of this study should be validated in further trials.

Onset of the neuromuscular block simulated in an anatomical model.

AIMS: The aim of this study was to develop a pharmacodynamic model for nondepolarizing muscle relaxants (neuromuscular blocking agents, NMBAs) based on anatomical, physiological, and pharmacological considerations and analyse whether the time to onset of the submaximal neuromuscular block (NMB) depends on the affinities of the NMBAs for the postsynaptic receptors or on the pharmacokinetic properties of the NMBAs. METHODS: A quantitative description of the development of neuromuscular block was achieved by formulating a pharmacodynamic model based on anatomical, physiological and pharmacological considerations. The principal characteristics of the model are: (1) Diffusion of the NMBAs out of the capillaries into the interstitial space of muscle and from there into the synaptic space of the motor end plates (2) Receptor concentration in the synaptic space of 300 microM and the total amount of receptors in 100 g muscle of between 1.43 x (10(-11) to 10(-10) mol. (3) Interaction of NMBAs with the receptors defined by the association (k(assoc) = 4 x 10(8) min-1 x M-1) and dissociation (k(dissoc) one of 4, 40, or 400 min-1) rate constants. RESULTS: The simulations demonstrated that different affinities of the NMBAs for the postsynaptic receptors (defined by k(assoc)/k(dissoc)) do not influence the onset of the submaximal NMB. On the other hand, the time to the peak submaximal NMB is dependent on the pharmacokinetic properties of the drugs: Those NMBAs that leave plasma rapidly produce the block faster but the fraction of the dose that contributes to the block is small. This fraction is larger for those NMBAs that produce NMB later and, hence, these NMBAs require smaller equieffective doses. CONCLUSIONS: We conclude that those muscle relaxants that produce neuromuscular block rapidly require larger equieffective doses due to their more rapid initial disappearance from plasma.

[Muscle relaxants. New substances and neuromuscular monitoring]. / Muskelrelaxanzien. Neue Substanzen und neuromuskuläres Monitoring.

INTRODUCTION: Recent developments in both the quantitative evaluation of neuromuscular blockade and new muscle relaxants are reviewed. With respect to nerve stimulation, neuromuscular recording, and definition of parameters, the results of the 1994 Copenhagen International Consensus Conference are highlighted. Future clinical studies should adhere to these standards. MUSCLE RELAXANTS: Rocuronium, cisatracurium, and mivacurium are new muscle relaxants that were released for clinical use in 1995/1996. Of these, rocuronium has the shortest time of onset, whereas its recovery characteristics closely resemble those of vecuronium. Rocuronium is five times less potent than vecuronium. Twice the ED95 of rocuronium provides good or excellent intubating conditions within 60 to 90 s. Slight vagolytic effects were reported following injection of 0.6 mg/kg rocuronium, while histamine release was not observed. Cisatracurium is one of the ten steroisomers of atracurium. It is five times as potent as the chiral mixture while having a similar pharmacodynamic and -kinetic profile. Up to eight times the ED95 did not cause significant histamine release or clinically relevant cardiovascular effects. Mivacurium is a short-acting nondepolarizing benzylisoquinoline muscle relaxant that undergoes rapid break-down by plasma cholinesterase (PChE). Its duration of action is about one-half as long as that of equipotent doses of atracurium and vecuronium and three times as long as succinylcholine. Mivacurium has a moderate histamine-releasing potential. In patients with atypical or reduced PChE activity, the duration of action of mivacurium is prolonged.

Effects of a hemoglobin-based oxygen carrier (HBOC-201) on hemodynamics and oxygen transport in patients undergoing preoperative hemodilution for elective abdominal aortic surgery.

We conducted a pilot study to evaluate the effects of HBOC-201, a bovine hemoglobin-based oxygen carrier, on hemodynamics and oxygen transport in patients undergoing preoperative hemodilution for elective abdominal aortic surgery. After induction of anesthesia and isovolemic hemodilution with 1 L of lactated Ringer's solution, 13 patients were randomly assigned to receive, within 30 min, 3 mL/kg of either HBOC-201 or 6% hydroxyethyl starch (HES). Monitored variables included invasive arterial and pulmonary artery pressures, arterial and mixed venous blood gases, and calculations of cardiac index (CI), systemic and pulmonary vascular resistance indices, oxygen delivery index (DO2I), oxygen consumption index (VO2I), and oxygen extraction ratio (O2ER). Thirty minutes after HBOC-201 infusion, mean arterial pressure, systemic vascular resistance index, and CI were 149% (P = 0.028), 169% (P = 0.046), and 75% (P = 0.46) of the preinfusion values, respectively. No significant changes were noticed in heart rate and pulmonary vascular resistance index. DO2I and VO2I, 30 min after the infusion of HBOC-201, were 79% (P = 0.046) and 76% (P = 0.028) of the preinfusion values, respectively, whereas CaO2 and O2ER remained unaffected. We conclude that HBOC-201, at a dose of 3 mL/kg, impairs oxygen delivery because of adverse effects on cardiac output.

A comparison of cisatracurium and atracurium: onset of neuromuscular block after bolus injection and recovery after subsequent infusion.

Cisatracurium is a new nondepolarizing muscle relaxant. In patients randomized to receive either cisatracurium (n = 40) or atracurium (n = 20) we compared the time course of neuromuscular block. The initial bolus dose of cisatracurium was 0.1 mg/kg, that of atracurium 0.5 mg/kg. Neuromuscular block, maintained with an infusion of either drug, was reversed with neostigmine 45 micrograms/kg and atropine 20 micrograms/kg in one half of the patients. Neuromuscular transmission was assessed by recording the mechanical twitch response to train-of-four nerve stimulation. Onset times were 3.1 +/- 1.0 min with cisatracurium and 2.3 +/- 1.1 min with atracurium (P = 0.008). The infusion rates for a 95% +/- 4% neuromuscular block were 1.5 +/- 0.4 micrograms.kg-1.min-1 for cisatracurium and 6.6 +/- 1.7 micrograms.kg-1.min-1 for atracurium, 3.3 times those of cisatracurium when referenced to the active cations. After the infusion, the spontaneous recovery intervals 25%-75% of 18 +/- 11 min and 18 +/- 8 min for cisatracurium and atracurium (P = 0.896) were shortened to 5 +/- 2 min and 4 +/- 3 min (P = 0.921) after neostigmine. While attributing different onset times also to differences in the initial doses, we conclude that time profiles for neuromuscular block of both muscle relaxants, when given in equipotent doses, are not different.

[Autologous blood transfusion in the Federal Republic of Germany--results of a questionnaire in 1993. 2. The use of autologous transfusion in the old and new federation]. / Autologe Bluttransfusion in der Bundesrepublik Deutschland--Ergebnisse einer Umfrage aus dem Jahre 1993. Teil 2: Die Verbreitung autologer Transfusionsverfahren in den alten und neuen Bundesländern.

In 1993, we conducted a postal survey to assess the use of autologous blood transfusion (ABT) in the Federal Republic of Germany after reunification. The results of this survey have already been reported in a previous paper, but without differentiation between the "old" and "new" states (former West Germany and former German Democratic Republic, respectively). In the present study, the data of our 1993 survey were further analysed to see if there were differences in the use of ABT between the "old" and "new" states. METHODS. The study is based on data of a 1993 postal survey of German hospitals. Details concerning the performance of the survey have been reported in a previous paper. Briefly, questionnaires were mailed to the anaesthesia departments of 400 randomly selected hospitals in the "old" states and 284 hospitals in the "new" states of the Federal Republic of Germany. The questionnaires contained 36 questions related to general information on the hospital and the use of ABT; 305 completed questionnaires were returned from the "old" states and 197 from the "new" states, response rates of 76% and 69%, respectively. For the present investigation, the responses of the hospitals of the "old" and "new" states were analysed separately. Frequency distributions of categorical variables were analysed by the chi-square test. Because of multiple testing, statistical significance was attained only at the 0.05% level (P < or = 0.0005). RESULTS. There were no significant differences between the "old" and "new" states with respect to hospital size by number of beds, percentage of general and specialised hospitals, and percentage of operations requiring blood transfusion. In both the "old" and "new" states, 9% of the responding hospitals maintained a hospital-based transfusion service, while the other depended on regional blood banks. Preoperative autologous blood donation (PABD) was performed at least "rarely" in 85% and 71% (P = 0.0001), and "mostly" in 20% and 10% (P = 0.0014) of the hospitals in the "old" and "new" states, respectively. Uniformly, the principal uses of PABD were for orthopaedic and cardiac surgery. In 62% and 27% (P < 0.0001) of those hospitals that reported performing PABD, the autologous blood service was run by the anaesthesia department. Preoperative plasmapheresis was performed in 14% and 8% (P = 0.008), and isovolaemic haemodilution in 82% and 56% (P < 0.0001) of the hospitals in the "old" and "new" states, respectively. Automated autotransfusion devices (cell savers) were available in 38% and 19% (P < 0.0001) of the hospitals, respectively. Simple collection devices for perioperative blood salvage were used in 17% and 15% (P = 0.24) of the hospitals in the "old" and "new" states, respectively. CONCLUSION. We conclude that ABT is more widely used in the "old" than the "new" states of the Federal Republic of Germany. ABT is regarded as a desirable alternative to homologous blood transfusion, and in the interest of equal standards of medical care throughout the nation, the use of ABT should be further promoted, especially in the "new" states of the Federal Republic of Germany.

[New muscle relaxants]. / Neue Muskelrelaxanzien.

Mivacurium is a short-acting nondepolarising muscle relaxant of the benzylisoquinoline type undergoing rapid breakdown by plasma cholinesterase. With 2.5 fold ED95, tracheal intubation can be accomplished within 2-3 min following injection. The ensuing DUR 25% (i.e. time from injection to 25% recovery of control twitch tension) is three times as long as with succinylcholine and about half as long as with equipotent doses of atracurium and vecuronium. The principal side effects of mivacurium are facial flushing and a transient fall in blood pressure due to a moderate histamine release following doses of 3-4 times the ED95. In patients with end stage liver or renal disease as well as in patients with atypical plasma cholinesterase the duration of action of mivacurium is prolonged. Rocuronium is a steroidal non-depolarising neuromuscular blocking agent chemically related to vecuronium. Compared with the latter, rocuronium is less potent, has a shorter onset of action, and no cumulative effects. Adequate intubating conditions are achieved within 60 to 90 s after i.v. injection of twice the ED95. Its elimination from the blood occurs primarily via liver uptake, while renal elimination is about 10 to 30%. Slight vagolytic effects are reported following injection of 0.6 mg/kg rocuronium, while histamine release is unlikely to occur. Atracurium is a mixture of ten stereoisomers. One of them, cis-atracurium, is five times as potent as the chiral mixture while having a similar pharmacodynamic and kinetic profile. It does not cause significant histamine release or clinically relevant cardiovascular effects at doses up to 8 times the ED95. Laudanosine release seems to be less with cis-atracurium than with atracurium.

Muscle relaxants: a clinical update.

The new nondepolarizing muscle relaxant rocuronium belongs to the chemical group of aminosteroidal muscle relaxants and is similar to vecuronium in its chemical structure and pharmacologic action. The principal clinical advantage of rocuronium over vecuronium is the short time to onset of the neuromuscular block. The two other new muscle relaxants, mivacurium and cis-atracurium, belong to the group of benzylisoquinoline muscle relaxants. Mivacurium is rapidly degraded in plasma and its principal characteristic is, hence, a short duration of action. Cis-atracurium is one of the 10 stereoisomers of atracurium. While its action is similar to that of atracurium, it does not release histamine and its administration is not accompanied by marked changes in blood pressure or heart rate. Even the simple tactile monitoring of the neuromuscular transmission enables the clinician to adjust the doses of these and other muscle relaxants to the needs of individual patients. Precise adjustment of the doses of muscle relaxants contributes to their safer clinical use by avoiding an excessively deep and unnecessarily prolonged neuromuscular block.

Changes in plasma cholinesterase activity and mivacurium neuromuscular block in response to normothermic cardiopulmonary bypass.

The effect of reduced plasma cholinesterase (ChE) activity in response to normothermic cardiopulmonary bypass (CPB) on mivacurium neuromuscular block was studied in nine patients anesthetized with propofol/fentanyl. Mivacurium was injected intravenously as an initial bolus of 150 micrograms/kg; repeat doses of 75 micrograms/kg were given when the evoked twitch tension attained 75% of control. With the institution of CPB, the previously normal ChE activity was reduced by 42% and remained low until the end of the procedure. The times of onset (time from the end of injection to maximum neuromuscular block) of the maintenance doses of mivacurium were 26% longer during than before or after CPB (P < 0.05). Their DUR25% (time from end of injection to recovery of neuromuscular transmission to 25% of control) were 13 +/- 3 min (means +/- SD) before, 14 +/- 4 min during, and 16 +/- 4 min (P < 0.05) after CPB. It is concluded, that, although markedly reducing the patient's previously normal ChE activity, normothermic CPB had little effect on the time characteristics of mivacurium neuromuscular block.

Alcuronium: a pharmacodynamic and pharmacokinetic update.

Alcuronium may be considered a muscle relaxant of historical rather than clinical significance. However, recent information from the manufacturer revealed its persisting clinical use in 26 countries worldwide. Thus, a pharmacodynamic-pharmacokinetic update appears mandatory. An intravenous (IV) single-bolus injection of alcuronium (0.25 mg/kg = ED95) was administered to 10 patients undergoing maxillofacial surgery during nitrous-oxide opioid anesthesia. Alcuronium neuromuscular block (evoked twitch tension), plasma concentration, and renal elimination (high-performance liquid chromatography [HPLC] assay) were measured during the 12-h after its administration. The time of onset, the time from end of injection to recovery to 25% of control twitch tension (DUR25%), and the recovery index were 2.2 +/- 1.2, 54 +/- 14, and 37 +/- 11 min, respectively (mean +/- SD). Two hours after the injection of alcuronium, partial recovery from the neuromuscular block had occurred from 100% to 26% +/- 24% depression of twitch tension, although less than 25% of the injected dose was recovered from the urine. The 12-h plasma concentration and urinary recovery were 0.1 +/- 0.08 mg/L (one-sixth of the 50% inhibitory concentration) and 61% +/- 20%, respectively. Recovery from neuromuscular block was dominated by intercompartmental distribution rather than by renal elimination. Since alcuronium does not undergo biodegradation, our data may serv as a reference for the complex pharmacokinetics of readily metabolized modern muscle relaxants. The long plasma half-life with slow excretion merits attention with respect to the erroneous original perception that alcuronium was an intermediate-acting muscle relaxant.

Mivacurium chloride--a comparative profile.

Mivacurium is a new nondepolarizing muscle relaxant of the benzylisoquinoline type. Its short duration of action is due to rapid breakdown by plasma cholinesterase. The dose of mivacurium which produces 95% inhibition of twitch response (ED95) is between 60 and 80 micrograms/kg. Thus, mivacurium is 0.8 times and four times as potent as vecuronium and atracurium, respectively. With 2-3 x ED95, tracheal intubation can be accomplished within 2.5 min of intravenous injection. The ensuing DUR25% (time from injection to 25% recovery of control twitch tension) is twice as long as with suxamethonium and about half as long as with equipotent doses of atracurium or vecuronium. For muscle relaxation during long surgical procedures, mivacurium has been used as a continuous infusion. The average 6-min recovery index after infusion of mivacurium is particularly favourable for flexible control of muscle paralysis, whereas the recovery indices after infusion of atracurium or vecuronium are 15-30 min. In conclusion, mivacurium will close the pharmacodynamic gap between suxamethonium and the nondepolarizing muscle relaxants of intermediate duration of action. It will probably also be a suitable alternative to suxamethonium in elective cases.