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1.
Br J Anaesth ; 113(5): 772-83, 2014 Nov.
Article in English | MEDLINE | ID: mdl-25326478

ABSTRACT

Fluid management during critical illness is a dynamic process that may be conceptualized as occurring in four phases: rescue, optimization, stabilization, and de-escalation (mobilization). The selection and administration of resuscitation fluids is one component of this complex physiological sequence directed at restoring depleted intravascular volume. Presently, the selection of i.v. fluid is usually dictated more by local practice patterns than by evidence. The debate on fluid choice has primarily focused on evaluating outcome differences between 'crystalloids vs colloids'. More recently, however, there is interest in examining outcome differences based on the chloride content of crystalloid solutions. New insights into the conventional Starling model of microvascular fluid exchange may explain that the efficacy of colloids in restoring and maintaining depleted intravascular volume is only moderately better than crystalloids. A number of investigator-initiated, high-quality, randomized controlled trials have demonstrated that modest improvements in short-term physiological endpoints with colloids have not translated into better patient-centred outcomes. In addition, there is substantial evidence that certain types of fluids may independently worsen patient-centred outcomes. These include hydroxyethyl starch and albumin solutions in selected patient populations. There is no evidence to support the use of other colloids. The use of balanced salt solutions in preference to 0.9% saline is supported by the absence of harm in large observational studies. However, there is no compelling randomized trial-based evidence demonstrating improved clinical outcomes with the use of balanced salt solutions compared with 0.9% saline at this time.


Subject(s)
Acute Disease/therapy , Fluid Therapy/methods , Critical Care/methods , Critical Illness/therapy , Dialysis , Humans
2.
Transplant Proc ; 44(5): 1336-40, 2012 Jun.
Article in English | MEDLINE | ID: mdl-22664011

ABSTRACT

BACKGROUND: Protein C is a natural thrombin antagonist produced by hepatocytes. Its levels are low in liver failure and predispose patients to increased risk for thrombosis. Little is known about the relationship between protein C activity and hepatic function after orthotopic liver transplantation (OLT). METHODS: We measured protein C activity of 41 patients undergoing liver transplantation by the Staclot method (normal range, 70%-130%) preoperatively and then daily on postoperative days (POD) 0-5. RESULTS: The mean protein C activity was low before OLT (34.3 ± 4.3%) and inversely correlated with the preoperative Model for End-Stage Liver Disease score (Spearman's r = -0.643; P < .0001). Mean activity increased significantly on POD 1 (58.9 ± 4.5%), and remained above preoperative levels through POD 5. Ten patients developed metabolic liver dysfunction defined by a serum total bilirubin >5 mg/dL on POD 7. These patients had significantly lower protein C activity from POD 3 (47.2 ± 9.6% vs 75.9 ± 5.8%; P = .01) to POD 5. Preoperative protein C activity correlated inversely with the severity of liver failure as indicated by preoperative MELD score. CONCLUSION: Protein C activity recovered rapidly in patients with good allograft function but remained significantly lower in patients who had limited metabolic function as evidenced by increased total bilirubin levels.


Subject(s)
Liver Failure/surgery , Liver Transplantation/adverse effects , Liver/surgery , Primary Graft Dysfunction/etiology , Protein C/metabolism , Aged , Bilirubin/blood , Biomarkers/blood , Blood Coagulation , Blood Coagulation Tests , Female , Humans , Liver/metabolism , Liver/physiopathology , Liver Failure/blood , Liver Failure/diagnosis , Male , Middle Aged , New York , Predictive Value of Tests , Primary Graft Dysfunction/blood , Primary Graft Dysfunction/diagnosis , Primary Graft Dysfunction/physiopathology , Severity of Illness Index , Time Factors , Treatment Outcome
3.
Br J Anaesth ; 103 Suppl 1: i57-65, 2009 Dec.
Article in English | MEDLINE | ID: mdl-20007991

ABSTRACT

The incidence of asthma is increasing worldwide, but morbidity and mortality are decreasing because of improvements in medical care. Although the incidence of severe perioperative bronchospasm is relatively low in asthmatics undergoing anaesthesia, when it does occur it may be life-threatening. The keys to an uncomplicated perioperative course are assiduous attention to detail in preoperative assessment, and maintenance of the anti-inflammatory and bronchodilatory regimens through the perioperative period. Potential trigger agents should be identified and avoided. Many routinely used anaesthetic agents have an ameliorative effect on airway constriction. Nonetheless, acute bronchospasm can still occur, especially at induction and emergence, and should be promptly and methodically managed.


Subject(s)
Asthma/complications , Bronchial Spasm/etiology , Intraoperative Complications , Perioperative Care/methods , Anesthesia/adverse effects , Anesthesia/methods , Asthma/drug therapy , Asthma/physiopathology , Bronchial Spasm/drug therapy , Bronchial Spasm/physiopathology , Bronchodilator Agents/therapeutic use , Humans
5.
Ann Thorac Surg ; 72(1): 272-4, 2001 Jul.
Article in English | MEDLINE | ID: mdl-11465200

ABSTRACT

Inhaled nitric oxide, a selective pulmonary vasodilator, has been used to improve arterial oxygenation in adult respiratory distress syndrome. To our knowledge, it has not been successfully used to treat this syndrome after major lung resection. We used nitric oxide to treat postpneumonectomy pulmonary edema with immediate and sustained improvement in oxygenation. The patient was successfully weaned from nitric oxide and extubated after 3 days of supportive therapy.


Subject(s)
Nitric Oxide/administration & dosage , Pneumonectomy , Postoperative Complications/drug therapy , Pulmonary Edema/drug therapy , Administration, Inhalation , Aged , Carcinoma, Squamous Cell/surgery , Humans , Lung Neoplasms/surgery , Male
8.
Curr Opin Anaesthesiol ; 14(6): 699-706, 2001 Dec.
Article in English | MEDLINE | ID: mdl-17019168

ABSTRACT

Recent publications regarding perioperative renal dysfunction provide a 'potpourri' of topics worthy of discussion. The risk of perioperative renal dysfunction is higher in patients with heart failure, but other pre-existing conditions, such as genetic polymorphism, may have prognostic implications. Evaluation of renal risk and protective interventions are discussed for a number of specific operative entities, including cardiac surgery (with or without cardiopulmonary bypass), aortic surgery and renal revascularization. New publications on a wide variety of nephrotoxic insults are presented, including antifibrinolytic agents, obstructive jaundice, prostaglandin inhibitors, cyclosporine A, radiocontrast dyes and volatile anesthetic agents. Renal transplantation is discussed as a specific entity. Finally, we discuss recent papers describing outcome in patients in chronic renal failure undergoing cardiac surgery.

9.
Crit Care Clin ; 17(4): 1015-27, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11762262

ABSTRACT

The authors have presented a template for a systematic approach to comforting critically ill patients that can be modified to suit institutional preferences. In this algorithm, the cause of patient discomfort is sought with the priority given to pain and then to anxiety. Special attention is directed to the identification of correctable causes of pain and anxiety with application of nonpharmacologic techniques or medications to control patient discomfort. This step is followed by subsequent reassessment of the need for sedation or anxiolysis and titration or discontinuation of therapy as able. The benefits of protocol-driven care are becoming increasingly evident, and the authors believe the algorithm outlined here provides a rational and practical approach to patient management. It also prompts the caregiver to reevaluate patients' needs and to keep to patients at target sedation levels. Doing so can promote cost effectiveness, reduce side effects caused by drugs, and decrease morbidity and ICU stay. Any treatment protocol or algorithm is simply a guide to therapy and cannot address every clinical situation. The importance of individualized care and physician or care team judgment must be emphasized.


Subject(s)
Analgesia , Conscious Sedation , Critical Illness/psychology , Intensive Care Units/standards , Algorithms , Anxiety , Clinical Protocols , Humans , Pain Measurement , Patient-Centered Care , Practice Guidelines as Topic
10.
Anesthesiol Clin North Am ; 18(4): 739-52, viii, 2000 Dec.
Article in English | MEDLINE | ID: mdl-11094688

ABSTRACT

Perioperative oliguria is common but rarely implies acute renal failure. We should interpret oliguria as a sign of intravascular hypovolemia and treat it as prerenal until proven otherwise. On the other hand, the absence of oliguria does not exclude acute renal failure. The most reliable clinical indicator of progressive renal dysfunction is a serial decline in creatinine clearance estimation, a measure of glomerular filtration rate.


Subject(s)
Oliguria/diagnosis , Oliguria/therapy , Postoperative Complications , Acute Kidney Injury/etiology , Algorithms , Animals , Diuretics/therapeutic use , Drug Resistance , Fluid Therapy , Humans , Intensive Care Units , Oliguria/etiology , Postoperative Complications/diagnosis , Postoperative Complications/therapy , Risk Factors
11.
Anesthesiol Clin North Am ; 18(4): 791-807, ix, 2000 Dec.
Article in English | MEDLINE | ID: mdl-11094691

ABSTRACT

Renal blood flow and renal perfusion pressure are regulated by two control mechanisms. The first, extrinsic, actually involves a complex interaction of vasomotor effects between opposing neurohormonal systems. The second, intrinsic mechanism, renal autoregulation, depends on changes in afferent arteriolar tone in response to the renal perfusion pressure itself. This article reviews these two mechanisms, how they normally respond to stress, and the clinical implications of certain situations in which these control mechanisms are disrupted.


Subject(s)
Homeostasis , Kidney Diseases/physiopathology , Renal Circulation/physiology , Vasomotor System/physiopathology , Cardiopulmonary Bypass/adverse effects , Humans , Kidney Diseases/chemically induced , Kidney Diseases/etiology , Kidney Tubular Necrosis, Acute/physiopathology , Liver Failure/complications , Liver Failure/physiopathology , Shock, Septic/complications , Shock, Septic/physiopathology , Vasoconstriction
12.
Anesthesiol Clin North Am ; 18(4): 863-82, x, 2000 Dec.
Article in English | MEDLINE | ID: mdl-11094695

ABSTRACT

Patients in end-stage renal disease and chronic liver failure present a number of challenges to the anesthesiologist. They may be chronically ill and debilitated and have the potential for multisystem organ dysfunction. To safely manage these patients we need to understand the benefits and limitations of dialysis and the altered pharmacology of commonly used anesthetic agents and perioperative medications in chronic renal failure.


Subject(s)
Anesthesia/methods , Kidney Failure, Chronic , Humans , Kidney Failure, Chronic/complications , Kidney Failure, Chronic/physiopathology , Kidney Failure, Chronic/therapy , Preoperative Care , Renal Dialysis
13.
Am J Respir Crit Care Med ; 162(4 Pt 1): 1361-5, 2000 Oct.
Article in English | MEDLINE | ID: mdl-11029345

ABSTRACT

In patients with acute respiratory distress syndrome (ARDS), permissive hypercapnia is a strategy to decrease airway pressures to prevent ventilator-induced lung damage by lowering tidal volumes and tolerating higher arterial carbon dioxide tension. However, in experimental studies hypercapnia impairs myocardial contractility and hemodynamic function. We investigated the effect of short-term permissive hypercapnia on myocardial contractility and hemodynamics in patients with ARDS. We hypothesized that the administration of tromethamine (THAM), a buffer which does not increase carbon dioxide production, would modify these changes. In 12 patients with ARDS, permissive hypercapnia was implemented for 2 h with a target Pa(CO(2))of 80 mm Hg. Patients were randomized to have respiratory acidosis corrected by THAM (pH-corrected group), or not corrected (pH-uncorrected group). Hemodynamic responses were measured, and transesophageal echocardiography (TEE) was used to determine myocardial contractility. Permissive hypercapnia resulted in significant decreases in systemic vascular resistance (SVR) and increases in cardiac output (Q). Myocardial contractility decreased in both groups but significantly less in the pH-corrected group (approximately 10%) than in the pH-uncorrected group (approximately 18%, p < 0.05). Mean arterial pressure decreased and mean pulmonary arterial pressure increased significantly only in the pH-uncorrected group. All values returned to baseline conditions 1 h after permissive hypercapnia was terminated. Our study demonstrates a reversible depression of myocardial contractility and hemodynamic alterations during rapid permissive hypercapnia which were attenuated by buffering with THAM. This may have applicability to the clinical strategy of permissive hypercapnia and allow the benefit of decreased airway pressures to be realized while minimizing the adverse hemodynamic effects of hypercapnic acidosis.


Subject(s)
Hypercapnia/drug therapy , Myocardial Contraction/drug effects , Respiratory Distress Syndrome/drug therapy , Tromethamine/administration & dosage , Acid-Base Equilibrium/drug effects , Acid-Base Equilibrium/physiology , Adult , Aged , Buffers , Carbon Dioxide/blood , Critical Care , Echocardiography/drug effects , Female , Hemodynamics/drug effects , Hemodynamics/physiology , Humans , Hypercapnia/physiopathology , Male , Middle Aged , Myocardial Contraction/physiology , Respiration, Artificial , Respiratory Distress Syndrome/physiopathology
14.
Anesthesiology ; 91(6): 1577-86, 1999 Dec.
Article in English | MEDLINE | ID: mdl-10598597

ABSTRACT

BACKGROUND: Recent years have seen the introduction of innovative additive therapies for acute respiratory distress syndrome. However, because there are no reliable predictors of response to a particular therapy, potential responders to a specific therapeutic intervention may be lost. Therefore, the authors evaluated the effect of a combined therapeutic approach on the survival of patients with acute respiratory distress syndrome, when treated according to a strict algorithm. METHODS: During a 2.5-yr period, 84 patients with acute respiratory distress syndrome were assigned to a standardized treatment protocol. Data analysis was performed by retrospective review of patient charts. Patients were treated using a stepwise treatment algorithm of pressure-controlled ventilation (peak airway pressure < 35 cm H2O), positive end-expiratory pressure (PEEP; 12-15 cm H2O), permissive hypercapnia, inhaled nitric oxide (5-20 ppm), and prone positioning. These interventions were termed "conventional therapy." Response to treatment was defined as a more than 20% increase in arterial oxygen tension (PaO2). Nonresponders were triaged to extracorporeal membrane oxygenation. RESULTS: The overall survival rate was 80%. All patients received conventional therapy up to 96 h; 71 responded to conventional therapy and 59 survived (83%). Thirteen patients (15%) did not respond to conventional therapy and underwent extracorporeal membrane oxygenation; 8 of these patients (62%) survived. For the group, the mean admission lung injury score was 3.3+/-0.5, the PaO2/fractional inspired oxygen tension (F(I)O2) ratio was 96+/-45, and the Acute Physiology and Chronic Health Evaluation (APACHE) II score was 18+/-6. CONCLUSIONS: The 80% overall survival rate achieved in this group of patients with severe acute respiratory distress syndrome may in part reflect the additive beneficial effects of combined treatment methods, such as airway pressure control, nitric oxide inhalation, prone position, and early triage of nonresponders to extracorporeal membrane oxygenation.


Subject(s)
Extracorporeal Membrane Oxygenation , Nitric Oxide/therapeutic use , Prone Position/physiology , Respiration, Artificial , Respiratory Distress Syndrome/therapy , APACHE , Administration, Inhalation , Adolescent , Adult , Aged , Child , Combined Modality Therapy , Electrocardiography , Female , Humans , Male , Middle Aged , Nitric Oxide/administration & dosage , Respiratory Distress Syndrome/physiopathology , Respiratory Function Tests , Survival Analysis
15.
Article in English | MEDLINE | ID: mdl-10352804

ABSTRACT

Physiologic hyperlactatemia must be distinguished from lactate acidosis (lactate > 5 mM/L, pH < 7.32). Sustained lactic acidosis, or changes in lactate in response to inotropic support, are useful predictors of mortality in severe sepsis and trauma, and superior to hemodynamic markers such as DO2 and VO2. Base deficit is a readily available surrogate for plasma lactate, and the addition of gastric tonometry enhances its predictive ability.


Subject(s)
Lactic Acid/blood , Sepsis/blood , Wounds and Injuries/blood , Acidosis, Lactic/blood , Biomarkers , Humans , Sepsis/diagnosis , Wounds and Injuries/diagnosis
16.
Anesth Analg ; 88(4): 853-6, 1999 Apr.
Article in English | MEDLINE | ID: mdl-10195537

ABSTRACT

UNLABELLED: Tramadol is an analgesic drug that is antagonized by alpha2-adrenoceptor antagonists, as well as opioid antagonists. We hypothesized that tramadol might produce effects on an axillary brachial plexus blockade similar to those of clonidine. We designed a prospective, controlled, double-blinded study to assess the impact of tramadol added to mepivacaine on the duration of an axillary brachial plexus blockade. After institutional approval and informed consent, 60 patients (ASA physical status I or II) scheduled for forearm and hand surgery after trauma under brachial plexus anesthesia were included in the study. Patients were randomly assigned to receive either 40 mL of mepivacaine 1% with 2 mL of isotonic sodium chloride solution (Group A, n = 20); 40 mL of mepivacaine 1% with 100 mg of tramadol (Group B, n = 20); or 40 mL of mepivacaine 1% with 2 mL of isotonic sodium chloride solution and 100 mg of tramadol i.v. (Group C, n = 20). Sensory block, motor block, and hemodynamics were recorded before and 5, 10, 30, 60, 120, 180, and 360 min after local anesthetic injection. Duration of sensory and motor block was significantly longer (P < 0.01; P < 0.05) in Group B (299 +/- 84 and 259 +/- 76 min) than in Group A (194 +/- 35 and 181 +/- 24 min) and Group C (187 +/- 35 and 179 +/- 16 min). There was no difference in onset of sensory and motor blockade among groups. Hemodynamics remained unchanged in all patients throughout the study period. We conclude that the addition of tramadol prolongs the duration of brachial plexus block without side effects. Tramadol may be an alternative to epinephrine or clonidine as an adjuvant to local anesthesia for an axillary block. IMPLICATIONS: This study demonstrates that the admixture of 100 mg of tramadol with mepivacaine 1% for brachial plexus block provides a pronounced prolongation of blockade without side effects. Our data support a specific analgesic effect of tramadol on peripheral nerves.


Subject(s)
Analgesics, Opioid , Anesthetics, Local , Brachial Plexus , Mepivacaine , Nerve Block/methods , Tramadol , Adult , Arm Injuries/surgery , Blood Pressure/drug effects , Double-Blind Method , Drug Combinations , Female , Hand Injuries/surgery , Heart Rate/drug effects , Humans , Male , Middle Aged , Time Factors
17.
Curr Opin Anaesthesiol ; 12(4): 473-9, 1999 Jul.
Article in English | MEDLINE | ID: mdl-17013354

ABSTRACT

Blood transfusion is an essential and ubiquitous component of medical therapy. Despite careful screening and processing, allogeneic blood still carries a small but definable risk of the transmission of severe viral disease and the induction of immunological reactions. The logistics of its storage and transport continue to present a challenge, and its dependence on human donors will always keep it a scarce resource. It is not surprising that in the latter half of the 20th century efforts to develop blood substitutes have gained increasing momentum.

18.
Acta Anaesthesiol Scand ; 42(10): 1227-30, 1998 Nov.
Article in English | MEDLINE | ID: mdl-9834810

ABSTRACT

BACKGROUND: To present the role of transesophageal echocardiography (TEE) in the diagnosis and management of catheter-related superior vena cava thrombosis. CASE HISTORY: A 42-year-old woman with severe Crohn's disease presented with septic shock and pulmonary embolism three weeks after emergency laparotomy and ileocolic resection for small-bowel perforation with peritonitis. Cardiopulmonary evaluation with ECG, pulmonary artery catheter and TEE demonstrated no evidence of acute myocardial ischemia or ventricular dysfunction; hemodynamic indices were consistent with severe sepsis. TEE revealed a large sheathing thrombus surrounding a central venous catheter used for parenteral nutrition. A spiral CT scan of the chest confirmed multiple peripheral pulmonary emboli. Treatment consisted of systemic anticoagulation and antibiotics. To avoid further pulmonary embolism, the central venous catheter was not removed until six days later under TEE monitoring, which revealed that the thrombus was firmly adherent to the superior vena cava. The patient made an uneventful recovery and was discharged from hospital on long-term anticoagulant therapy. CONCLUSION: In a case of catheter-induced superior vena cava thrombosis with septicemia and pulmonary embolism, bedside TEE was very helpful to make the correct diagnosis early, assess thrombus size during anticoagulation, and monitor cardiac performance and thrombus disposition during central venous catheter removal.


Subject(s)
Catheterization, Central Venous/instrumentation , Echocardiography, Transesophageal , Vena Cava, Superior/diagnostic imaging , Venous Thrombosis/diagnostic imaging , Adult , Anti-Bacterial Agents , Anticoagulants/therapeutic use , Catheterization, Central Venous/adverse effects , Catheters, Indwelling/adverse effects , Crohn Disease/surgery , Drug Therapy, Combination/therapeutic use , Female , Humans , Ileal Diseases/surgery , Intestinal Perforation/surgery , Laparotomy , Parenteral Nutrition/adverse effects , Parenteral Nutrition/instrumentation , Peritonitis/surgery , Postoperative Complications , Pulmonary Embolism/diagnostic imaging , Pulmonary Embolism/drug therapy , Pulmonary Embolism/etiology , Shock, Septic/drug therapy , Shock, Septic/etiology , Tomography, X-Ray Computed , Venous Thrombosis/drug therapy , Venous Thrombosis/etiology
19.
Anesthesiology ; 89(6): 1401-6, 1998 Dec.
Article in English | MEDLINE | ID: mdl-9856714

ABSTRACT

BACKGROUND: The response to inhaled nitric oxide and prone positioning was investigated in 47 patients with adult respiratory distress syndrome to test the hypothesis that inhalation of nitric oxide when in the prone position would result in additive improvement in oxygenation. METHODS: The authors prospectively studied patients of both genders who were 15 to 75 yr old and had adult respiratory distress syndrome confirmed by computed tomography (lung injury score, 3.1+/-1). RESULTS: Compared with baseline values in the supine position (T1), inhalation of 10 ppm nitric oxide for 1 h (T2) decreased the mean pulmonary artery pressure from 33+/-9 mmHg to 28+/-6 mmHg (P < 0.05; T2 vs. T1) and increased the ratio of the partial pressure of oxygen in arterial blood (PaO2) to inspired oxygen concentration (FiO2) from 115 (median first quartile [Q1] 97, median third quartile [Q3] 137) to 148 (Q1 132, Q3 196) (P < 0.05; T2 vs. T1). Cessation of nitric oxide brought the values back to baseline (T3). Two hours of prone positioning (T4) significantly increased the PaO2:FiO2 ratio (T4 vs. T3). However, after an additional hour of nitric oxide inhalation in the prone position (T5), a significant decrease of the venous admixture (from 33+/-6% to 25+/-6%; P < 0.05) and an increase of the PaO2:FiO2 ratio (from 165 [Q1 129, Q3 216] to 199 [Q1 178, Q3 316] [P < 0.05; T5 vs. T4]) were observed. CONCLUSIONS: In patients with isolated severe adult respiratory distress syndrome, inhalation of nitric oxide in the prone position significantly improved oxygenation compared with nitric oxide inhalation in the supine position or in the prone position without nitric oxide. The combination of the prone position with nitric oxide inhalation in the treatment of severe adult respiratory distress syndrome should be considered.


Subject(s)
Nitric Oxide/therapeutic use , Oxygen Inhalation Therapy , Prone Position/physiology , Respiratory Distress Syndrome/prevention & control , Adolescent , Adult , Aged , Blood Gas Analysis , Female , Humans , Male , Middle Aged , Oxygen/blood , Prospective Studies , Pulmonary Circulation/drug effects , Respiratory Distress Syndrome/diagnostic imaging , Respiratory Distress Syndrome/physiopathology , Respiratory Function Tests , Supine Position/physiology , Tomography, X-Ray Computed
20.
Anesthesiology ; 89(6): 1418-29, 1998 Dec.
Article in English | MEDLINE | ID: mdl-9856717

ABSTRACT

BACKGROUND: Midazolam is commonly used for short-term postoperative sedation of patients undergoing cardiac surgery. The purpose of this multicenter study was to characterize the pharmacokinetics and intersubject variability of midazolam in patients undergoing coronary artery bypass grafting. METHODS: With institutional review board approval, 90 consenting patients undergoing coronary artery bypass grafting were enrolled at three study centers. All subjects received sufentanil and midazolam via target-controlled infusions. After operation, midazolam was titrated to maintain deep sedation for at least 2 h. It was then titrated downward to decrease sedation for a minimum of 4 h more and was discontinued before tracheal extubation. Arterial blood samples were taken throughout the study and were assayed for midazolam and 1-hydroxymidazolam. Midazolam population pharmacokinetic parameters were estimated using NONMEM. Cross-validation was used to estimate the performance of the model. RESULTS: The pharmacokinetics of midazolam were best described by a simple three-compartment mammillary model. Typical pharmacokinetic parameters were V1 = 32.2 l, V2 = 53 l, V3 = 245 l, Cl1 = 0.43 l/min, Cl2 = 0.56 l/min, and Cl3 = 0.39 l/min. The calculated elimination half-life was 15 h. The median absolute prediction error was 25%, with a bias of 1.4%. The performance in the cross-validation was similar. Midazolam metabolites were clinically insignificant in all patients. CONCLUSIONS: The intersubject variability and predictability of the three-compartment pharmacokinetic model are similar to those of other intravenous anesthetic drugs. This multicenter study did not confirm previous studies of exceptionally large variability of midazolam pharmacokinetics when used for sedation in intensive care settings.


Subject(s)
Coronary Artery Bypass , Hypnotics and Sedatives/pharmacokinetics , Midazolam/pharmacokinetics , Adult , Aged , Female , Hemodynamics/physiology , Humans , Hypnotics and Sedatives/administration & dosage , Hypnotics and Sedatives/blood , Infusions, Intravenous , Male , Midazolam/administration & dosage , Midazolam/blood , Middle Aged , Models, Biological , Postoperative Care/methods , Reproducibility of Results , Respiration, Artificial
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