Showing papers in "Anesthesiology in 2001"

Pathophysiology, Clinical Manifestations, and Prevention of Ischemia-Reperfusion Injury

Abstract: ISCHEMIA contributes to the pathophysiology of many conditions faced by anesthesiologists, including myocardial infarction, peripheral vascular insufficiency, stroke, and hypovolemic shock. Although restoration of blood flow to an ischemic organ is essential to prevent irreversible cellular injury, reperfusion per se may augment tissue injury in excess of that produced by ischemia alone. For example, the histologic changes of injury after 3 h of feline intestinal ischemia followed by 1 h of reperfusion are far worse than the changes observed after 4 h of ischemia alone. Cellular damage after reperfusion of previously viable ischemic tissues is defined as ischemia–reperfusion (I-R) injury. Ischemia–reperfusion associated with thrombolytic therapy, organ transplantation, coronary angioplasty, aortic cross-clamping, or cardiopulmonary bypass results in local and systemic inflammation. If severe enough, the inflammatory response after I-R may result in the systemic inflammatory response syndrome or multiple organ dysfunction syndrome (MODS), which account for 30–40% of the mortality in tertiary referral intensive care units. Thus, I-R injury may extend beyond the ischemic area at risk to include injury of remote, nonischemic organs.

Complications and treatment of mild hypothermia

Abstract: THE combination of anesthetic-induced impairment of thermoregulatory control and exposure to a cool operating room environment makes most surgical patients hypothermic. Several prospective, randomized trials have demonstrated various hypothermia-induced complications. There is no widely accepted definition for the term mild hypothermia. Furthermore, the term is not even used consistently in the literature. For the purpose of this review, mild hypothermia refers to core temperatures between 34 and 36°C.

Acute and nonacute complications associated with interscalene block and shoulder surgery: a prospective study.

Abstract: BackgroundThe incidence, etiology, and evolution of complications after interscalene brachial plexus block (ISB) are not well-known. The authors prospectively monitored 521 patients for complications during the first 9 months after ISB.MethodsA total of 521 adults scheduled for elective shoulder sur

Thoracic paravertebral block.

Abstract: Thoracic paravertebral blocks can be used to provide analgesia for unilateral trunk surgeries. Ultrasound-guided approaches for needle tip placement and injection monitoring are described. Anterior displacement of the pleura occurs with injection of local anesthetic in the paravertebral space.

The Visual Analog Scale for Pain: Clinical Significance in Postoperative Patients

Abstract: Background The visual analog scale is widely used in research studies, but its connection with clinical experience outside the research setting and the best way to administer the VAS forms are not well established This study defines changes in dosing of intravenous patient-controlled analgesia as a

Comparison of Closed-loop Controlled Administration of Propofol Using Bispectral Index as the Controlled Variable versus “Standard Practice” Controlled Administration

Abstract: BackgroundThis report describes a new closed-loop control system for propofol that uses the Bispectral Index (BIS) as the controlled variable in a patient-individualized, adaptive, model-based control system, and compares this system with manually controlled administration of propofol using hemodyna

Risk factors for perioperative adverse respiratory events in children with upper respiratory tract infections

Abstract: BackgroundAnesthesia for the child who presents for surgery with an upper respiratory infection (URI) presents a challenge for the anesthesiologist. The current prospective study was designed to determine the incidence of and risk factors for adverse respiratory events in children with URIs undergoi

Mechanism-based pain diagnosis: issues for analgesic drug development.

Abstract: ENORMOUS progress is currently being made by the exploitation of modern neurobiologic techniques in the elucidation of mechanisms that may contribute to the pathogenesis of pain. These indicate that pain can be generated in multiple ways at a number of different sites that may coexist between and across diverse disease states. Molecular biologic techniques are contributing to the analysis of pain mechanisms and are leading to the discovery of new targets, which are being used in high throughput screens by the pharmaceutical industry for the discovery of highly specific small molecules as potential novel analgesics. The discovery of targets specific to particular pain mechanisms will soon enable therapy to be targeted specifically at those mechanisms. This raises several problems: how to identify the mechanisms in an individual patient, how to test for the efficacy of a compound that may alter only one component of a complex syndrome that involves multiple mechanisms, and how to test for interaction between two different compounds targeted at two independent mechanisms. Clinical studies suggest that within conventional diagnostic groups of chronic pain patients, there are subgroups with differing responses to drug treatment, and yet the clinical development of new analgesic drugs has ignored this mechanistic heterogeneity. Trials that select patients based only on a disease may produce a false-negative result, with the nonresponders diluting out the benefit in the subgroup with the targeted mechanism. In this review, we sketch a research agenda that might move us toward a mechanism-based analgesic development. First, it is necessary to consider the following questions: To what degree can clinicians directly assess pain mechanisms in patients? What is the evidence from controlled clinical trials that variation in analgesic response between patients can be explained by disease or syndrome, tissue of pain origin, or symptom-based assessment of pain mechanisms? How should analgesic development pathways be revised to most efficiently demonstrate the spectrum of efficacy of a new drug? What types of collaborations between academic pain researchers, industry, government research funders, and regulators can hasten the potential clinical benefits of mechanism-based pain treatment?

Use of the intubating LMA-Fastrach in 254 patients with difficult-to-manage airways.

Abstract: Background The laryngeal mask airway (LMA™; LMA North America, Inc., San Diego, CA) has a well-established role in the emergency and elective treatment of patients with difficult-to-manage airways (DA). In this study, the authors report their clinical experience with the intubating LMA (LMA-Fastrach

Efficacy of a Simple Intraoperative Transfusion Algorithm for Nonerythrocyte Component Utilization after Cardiopulmonary Bypass

Abstract: BackgroundAbnormal bleeding after cardiopulmonary bypass (CPB) is a common complication of cardiac surgery, with important health and economic consequences. Coagulation test–based algorithms may reduce transfusion of non-erythrocyte allogeneic blood in patients with abnormal bleeding.MethodsThe auth

Preoperative Intradermal Acupuncture Reduces Postoperative Pain, Nausea and Vomiting, Analgesic Requirement, and Sympathoadrenal Responses

Abstract: Background: In a controlled and double-blind study, the authors tested the hypothesis that preoperative insertion of intradermal needles at acupoints 2.5 cm from the spinal vertebrae (bladder meridian) provide satisfactory postoperative analgesia. Methods: The authors enrolled patients scheduled for elective upper and lower abdominal surgery. Before anesthesia, patients undergoing each type of surgery were randomly assigned to one of two groups: acupuncture (n 5 50 and n 5 39 for upper and lower abdominal surgery, respectively) or control (n 5 48 and n 5 38 for upper and lower abdominal surgery, respectively). In the acupuncture group, intradermal needles were inserted to the left and right of bladder meridian 18 ‐24 and 20 ‐26 in upper and lower abdominal surgery before induction of anesthesia, respectively. Postoperative analgesia was maintained with epidural morphine and bolus doses of intravenous morphine. Consumption of intravenous morphine was recorded. Incisional pain at rest and during coughing and deep visceral pain were recorded during recovery and for 4 days thereafter on a four-point verbal rating scale. We also evaluated time-dependent changes in plasma concentrations of cortisol and catecholamines. Results: Starting from the recovery room, intradermal acupuncture increased the fraction of patients with good pain relief as compared with the control (P < 0.05). Consumption of supplemental intravenous morphine was reduced 50%, and the incidence of postoperative nausea was reduced 20 ‐30% in the acupuncture patients who had undergone either upper or lower abdominal surgery (P < 0.01). Plasma cortisol and epinephrine concentrations were reduced 30 ‐50% in the acupuncture group during recovery and on the first postoperative day (P < 0.01). Conclusion: Preoperative insertion of intradermal needles reduces postoperative pain, the analgesic requirement, and opioid-related side effects after both upper and lower abdominal surgery. Acupuncture analgesia also reduces the activation of the sympathoadrenal system that normally accompanies surgery. EPIDURAL analgesia or patient-controlled analgesia relieves postoperative pain in most patients undergoing abdominal surgery. However, analgesic drugs are expensive, and opioid analgesics are associated with complications, including drowsiness, pruritus, nausea and vomiting, and respiratory depression. Even a small reduction in the requirement for opioid analgesics is thus likely to be beneficial. Among the potential methods of reducing perioperative pain is acupuncture. 1‐5 In traditional Chinese theory, there is a series of acupoints called viscera-associated points. Among them are points located 2.5 cm from the spinal vertebrae (bladder meridian [BL]). The viscera-associated BL acupoints are mainly located on middle and lower thoracic vertebrae for upper abdominal organs and on lower thoracic to lumbar vertebrae for lower abdominal organs. Stimulation of these points reduces pain induced by visceral dysfunction. Acupuncture to these points may thus alleviate pain after abdominal surgery. However, traditional needle acupuncture cannot easily be performed at these sites because it would interfere with operative maneuvers and require unusual positioning during recovery. An alternative is insertion of fine intradermal needles. These needles are virtually painless; they can be inserted preoperatively and then maintained in position with adhesive tape throughout surgery and for several postoperative days. An excellent objective measure of postoperative pain

Attenuation of the tumor-promoting effect of surgery by spinal blockade in rats

Abstract: Background The perioperative period is characterized by a state of immunosuppression, which was shown in animal studies to underlie the promotion of tumor metastasis by surgery. As this immunosuppression is partly ascribed to the neuroendocrine stress response, the authors hypothesized that spinal blockade, known to attenuate this response, may reduce the tumor-promoting effect of surgery. Methods Fischer-344 rats were subjected to a laparotomy during general halothane anesthesia alone or combined with either systemic morphine (10 mg/kg) or spinal block using bupivacaine (50 microg) with morphine (10 microg). Control groups were either anesthetized or undisturbed. Blood was drawn 5 h after surgery to assess number and activity of natural killer cells, or rats were inoculated intravenously with MADB106 adenocarcinoma cells, which metastasize only to the lungs. Metastatic development was assessed by quantifying lung retention of tumor cells 24 h after inoculation or by counting pulmonary metastases 3 weeks later. Results Laparotomy conducted during general anesthesia alone increased lung tumor retention up to 17-fold. The addition of spinal block reduced this effect by 70%. The number of metastases increased from 16.7 +/- 10.5 (mean +/- SD) in the control group to 37.2 +/- 24.4 after surgery and was reduced to 10.5 +/- 4.7 during spinal block. Systemic morphine also reduced the effects of surgery, but to a lesser degree. Natural killer cell activity was suppressed to a similar extent by surgery and by anesthesia alone. Conclusions The addition of spinal blockade to general halothane anesthesia markedly attenuates the promotion of metastasis by surgery.

Effectiveness of epidural blood patch in the management of post-dural puncture headache.

Abstract: BackgroundLumbar epidural blood patch (EBP) is a common treatment of post–dural puncture headache, but its effectiveness and mode of action remain a matter of debate. The aim of this study was to assess both the effectiveness and the predictive factors of failure of EBP on severe post–dural puncture

Randomized Controlled Trial of Total Intravenous Anesthesia with Propofol versus Inhalation Anesthesia with Isoflurane-Nitrous Oxide Postoperative Nausea and Vomiting and Economic Analysis

Abstract: BackgroundTo assess the incidence of postoperative nausea and vomiting after total intravenous anesthesia (TIVA) with propofol versus inhalational anesthesia with isoflurane–nitrous oxide, the authors performed a randomized trial in 2,010 unselected surgical patients in a Dutch academic institution.

Bispectral index monitoring during sedation with sevoflurane, midazolam, and propofol.

Abstract: (PK 5 0.87 6 0.11, 0.76 6 0.01, and 0.69 6 0.02, respectively; P < 0.05). At 10 min after the procedure, 76, 48, and 24% of sevoflurane, propofol, midazolam patients, respectively, returned to baseline Digit Symbol Substitution scores (P < 0.05). Excitement‐disinhibition occurred in 70, 36, and 5% of sevoflurane, propofol, and midazolam patients, respectively (P < 0.05). Conclusion: Individual BIS scores demonstrate significant variability, making it difficult to predict sedation depth. The relation between BIS and sedation depth may not be independent of anesthetic agent. Quality of recovery was similar between drugs, but excitement occurred frequently with sevoflurane. THE Bispectral Index (BIS) has been used as a measure of the hypnotic effects of anesthetic agents. Although more commonly used as a measure of hypnosis during general anesthesia, BIS has also been used during sedation. BIS has been used to evaluate depth of sedation with propofol, 1,2 midazolam, 3 and sevoflurane. 4,5 Specifically, BIS has been evaluated for its ability to predict response to

American Society of Anesthesiologists Physical Status Classification System Is Not a Risk Classification System

Abstract: American Society of Anesthesiologists Physical Status Classification System Is Not a Risk Classification System William Owens; Anesthesiology

Current issues in spinal anesthesia

Abstract: Spinal anesthesia is an old, simple, and popular anesthetic technique, yet much remains unknown regarding pertinent anatomy, physiology, and pharmacology. Investigations into physiologic effects of spinal anesthesia reveal complex actions on multiple organ systems. New local anesthetics, analgesic additives, and techniques are being investigated for different applications as the practice of medicine focuses on outpatient care. Safety of spinal agents and complications from spinal anesthesia continue to be examined and re-examined to improve safety. Further study will be needed to fully resolve these issues and to further understand and improve the clinical use of spinal anesthesia.

Double-masked Randomized Trial Comparing Alternate Combinations of Intraoperative Anesthesia and Postoperative Analgesia in Abdominal Aortic Surgery

Abstract: Background: Improvement in patient outcome and reduced use of medical resources may result from using epidural anesthesia and analgesia as compared with general anesthesia and intravenous opioids, although the relative importance of intraoperative versus postoperative technique has not been studied. This prospective, double-masked, randomized clinical trial was designed to compare alternate combinations of intraoperative anesthesia and postoperative analgesia with respect to postoperative outcomes in patients undergoing surgery of the abdominal aorta. Methods: One hundred sixty-eight patients undergoing surgery of the abdominal aorta were randomly assigned to receive either thoracic epidural anesthesia combined with a light general anesthesia or general anesthesia alone intraoperatively and either intravenous or epidural patient-controlled analgesia postoperatively (four treatment groups). Patient-controlled analgesia was continued for at least 72 h. Protocols were used to standardize perioperative medical management and to preserve masking intraoperatively and postoperatively. A uniform surveillance strategy was used for the identification of prospectively defined postoperative complications. Outcome evaluation included postoperative hospital length of stay, direct medical costs, selected postoperative morbidities, and postoperative recovery milestones. Results: Length of stay and direct medical costs for patients surviving to discharge were similar among the four treatment groups. Postoperative outcomes were similar among the four treatment groups with respect to death, myocardial infarction, myocardial ischemia, reoperation, pneumonia, and renal failure. Epidural patient-controlled analgesia was associated with a significantly shorter time to extubation (P = 0.002). Times to intensive care unit discharge, ward admission, first bowel sounds, first flatus, tolerating clear liquids, tolerating regular diet, and independent ambulation were similar among the four treatment groups. Postoperative pain scores were also similar among the four treatment groups. Conclusions: In patients undergoing surgery of the abdominal aorta, thoracic epidural anesthesia combined with a light general anesthesia and followed by either intravenous or epidural patient-controlled analgesia, offers no major advantage or disadvantage when compared with general anesthesia alone followed by either intravenous or epidural patient-controlled analgesia.

Opioid peptide-expressing leukocytes: identification, recruitment, and simultaneously increasing inhibition of inflammatory pain.

Abstract: BackgroundInflammatory pain can be effectively controlled by an interaction of opioid receptors on peripheral sensory nerve terminals with opioid peptides released from immune cells upon stressful stimulation. To define the source of opioid peptide production, we sought to identify and quantify popu

The effect of prone positioning on intraocular pressure in anesthetized patients.

Abstract: BACKGROUND Ocular perfusion pressure is commonly defined as mean arterial pressure minus intraocular pressure (IOP). Changes in mean arterial pressure or IOP can affect ocular perfusion pressure. IOP has not been studied in this context in the prone anesthetized patient. METHODS After institutional human studies committee approval and informed consent, 20 patients (American Society of Anesthesiologists physical status I-III) without eye disease who were scheduled for spine surgery in the prone position were enrolled. IOP was measured with a Tono-pen XL handheld tonometer at five time points: awake supine (baseline), anesthetized (supine 1), anesthetized prone (prone 1), anesthetized prone at conclusion of case (prone 2), and anesthetized supine before wake-up (supine 2). Anesthetic protocol was standardized. The head was positioned with a pinned head-holder. Data were analyzed with repeated-measures analysis of variance and paired t test. RESULTS Supine 1 IOP (13 +/- 1 mmHg) decreased from baseline (19 +/- 1 mmHg) (P < 0.05). Prone 1 IOP (27 +/- 2 mmHg) increased in comparison with baseline (P < 0.05) and supine 1 (P < 0.05). Prone 2 IOP (40 +/- 2 mmHg) was measured after 320 +/- 107 min in the prone position and was significantly increased in comparison with all previous measurements (P < 0.05). Supine 2 IOP (31 +/- 2 mmHg) decreased in comparison with prone 2 IOP (P < 0.05) but was relatively elevated in comparison with supine 1 and baseline (P < 0.05). Hemodynamic and ventilatory parameters remained unchanged during the prone period. CONCLUSIONS Prone positioning increases IOP during anesthesia. Ocular perfusion pressure could therefore decrease, despite maintenance of normotension.

Intracuff Pressure and Tracheal MorbidityInfluence of Filling Cuff with Saline during Nitrous Oxide Anesthesia

Abstract: Background: Diffusion of nitrous oxide into the cuff of the endotracheal tube results in an increase in cuff pressure. Excessive endotracheal tube cuff pressure may impair tracheal mucosal perfusion and cause tracheal damage and sore throat. Filling the cuff of the endotracheal tube with saline instead of air prevents the increase in cuff pressure due to nitrous oxide diffusion. This method was used to test whether tracheal morbidity is related to excess in tracheal cuff pressure during balanced anesthesia. Methods: Fifty patients with American Society of Anesthesiologists physical status I or II were randomly allocated to two groups with endotracheal tube cuffs initially inflated to 20-30 cm H 2 O with either air (group A) or saline (group S). Anesthesia was maintained with isoflurane and nitrous oxide. At the time of extubation, a fiberoptic examination of the trachea was performed by an independent observer, and abnormalities of tracheal mucosa at the level of the cuff contact area were scored. Patients assessed their symptoms (sore throat, dysphagia, and hoarseness) at the time of discharge from the postanesthesia care unit and 24 h after extubation on a 101-point numerical rating scale. Results: Cuff pressure increased gradually during anesthesia in group A but remained stable in group S. The incidence of sore throat was greater in group A than in group S in the postanesthesia care unit (76 vs. 20%) and 24 h after extubation (42 vs. 12%; P < 0.05). Tracheal lesions at time of extubation were seen in all patients of group A and in eight patients (32%) of group S (P < 0.05). Conclusion: Excess in endotracheal tube cuff pressure during balanced anesthesia due to nitrous oxide diffusion into this closed gas space causes sore throat that is related to tracheal mucosal erosion.

Changes in blood volume and hematocrit during acute preoperative volume loading with 5% albumin or 6% hetastarch solutions in patients before radical hysterectomy.

Abstract: BackgroundThe impact of acute preoperative volume loading with colloids on blood volume has not been investigated sufficiently.MethodsBefore surgery, in 20 patients undergoing major gynecologic procedures, volume loading was performed during anesthesia by infusing approximately 20 ml/kg of colloid a

Randomized study comparing the "sniffing position" with simple head extension for laryngoscopic view in elective surgery patients.

Abstract: Background: The “sniffing position” is recommended for optimization of glottic visualization under direct laryngoscopy. However, no study to date has confirmed its superiority over simple head extension. In a prospective, randomized study, the authors compared the sniffing position with simple head extension in orotracheal intubation. Methods: The study included 456 consecutive patients. The sniffing position was obtained by placement of a 7-cm cushion under the head of the patient. The extension position was obtained by simple head extension. The anesthetic procedure included two laryngoscopies without paralysis: the first was used for topical glottic anesthesia. During the second direct laryngoscopy, intubation of the trachea was performed. The head position was randomized as follows: group A was in the sniffing position during the first laryngoscopy and the extension position during the second; group B was in the extension position during the first laryngoscopy and the sniffing position during the second. Glottic exposure was assessed by the Cormack scale. Results: The sniffing position improved glottic exposure (decreased the Cormack grade) in 18% of patients and worsened it (increased the Cormack grade) in 11% of patients, in comparison with simple extension. The Cormack grade distribution was not significantly modified between the two groups. Multivariate analysis showed that reduced neck mobility and obesity were independently related to improvement in laryngoscopic view with application of the sniffing position. Conclusions: Routine use of the sniffing position appears to provide no significant advantage over simple head extension for tracheal intubation in this setting. The sniffing position appears to be advantageous in obese and head extension–limited patients.

Cytochrome P-450 2B6 Is Responsible for Interindividual Variability of Propofol Hydroxylation by Human Liver Microsomes

Abstract: BackgroundOxidation of propofol to 4-hydroxypropofol represents a significant pathway in the metabolism of this anesthetic agent in humans. The aim of this study was to identify the principal cytochrome P-450 (CYP) isoforms mediating this biotransformation.MethodsPropofol hydroxylation activities an

A new model of electrically evoked pain and hyperalgesia in human skin: the effects of intravenous alfentanil, S(+)-ketamine, and lidocaine.

Abstract: BackgroundThe authors used the analgesics alfentanil, S (+)-ketamine, and systemic lidocaine to examine a new human model of experimental pain and hyperalgesia.MethodsTranscutaneous electrical stimulation at a high current density (5 Hz, 67.5 ± 6.6 mA) was used to provoke acute pain (numeric rating

Fiberoptic orotracheal intubation on anesthetized patients: do manipulation skills learned on a simple model transfer into the operating room?

Abstract: BackgroundWith increasing pressure to use operating room time efficiently, opportunities for residents to learn fiberoptic orotracheal intubation in the operating room have declined. The purpose of this study was to determine whether fiberoptic orotracheal intubation skills learned outside the opera

Evidence for susceptibility to malignant hyperthermia in patients with exercise-induced rhabdomyolysis.

Abstract: BackgroundMalignant hyperthermia (MH), heat stroke, and exercise-induced rhabdomyolysis (ER) were suspected to be related syndromes. However, it is not known whether individuals with history of ER have an increased incidence of susceptibility to MH. To establish an association between ER and suscept

Magnesium Sulfate Does Not Reduce Postoperative Analgesic Requirements

Abstract: BackgroundBecause magnesium blocks the N-methyl-d-aspartate receptor and its associated ion channels, it can prevent central sensitization caused by peripheral nociceptive stimulation. However, transport of magnesium from blood to cerebrospinal fluid (CSF) across the blood–brain barrier is limited i

Epidural Lidocaine Decreases Sevoflurane Requirement for Adequate Depth of Anesthesia as Measured by the Bispectral Index ® Monitor

Abstract: BACKGROUND Epidural anesthesia potentiates sedative drug effects and decreases minimum alveolar concentration (MAC). The authors hypothesized that epidural anesthesia also decreases the general anesthetic requirements for adequate depth of anesthesia as measured by Bispectral Index (BIS). METHODS After premedication with 0.02 mg/kg midazolam and 1 microg/kg fentanyl, 30 patients aged 20-65 yr were randomized in a double-blinded fashion to receive general anesthesia with either intravenous saline placebo or intravenous lidocaine control (1-mg/kg bolus dose; 25 microg x kg(-1) x min(-1)). A matched group was prospectively assigned to receive epidural lidocaine (15 ml; 2%) with intravenous saline placebo. All patients received 4 mg/kg thiopental and 1 mg/kg rocuronium for tracheal intubation. After 10 min of a predetermined end-tidal sevoflurane concentration, BIS was measured. The ED50 of sevoflurane for each group was determined by up-down methodology based on BIS less than 50 (MAC(BIS50)). Plasma lidocaine concentrations were measured. RESULTS The MAC(BIS50) of sevoflurane (0.59% end tidal) was significantly decreased with lidocaine epidural anesthesia compared with general anesthesia alone (0.92%) or with intravenous lidocaine (1%; P < 0.0001). Plasma lidocaine concentrations in the intravenous lidocaine group (1.9 microg/ml) were similar to those in the epidural lidocaine group (2.0 microg/ml). CONCLUSIONS Epidural anesthesia reduced by 34% the sevoflurane required for adequate depth of anesthesia. This effect was not a result of systemic lidocaine absorbtion, but may have been caused by deafferentation by epidural anesthesia or direct rostral spread of local anesthetic within the cerebrospinal fluid. Lower-than-expected concentrations of volatile agents may be sufficient during combined epidural-general anesthesia.

A double-blind, randomized comparison of IV lorazepam versus midazolam for Sedation of ICU patients via a pharmacologic model

Abstract: Background: Benzodiazepines, such as lorazepam and midazolam, are frequently administered to surgical intensive care unit (ICU) patients for postoperative sedation. To date, the pharmacology of lorazepam in critically ill patients has not been described. The aim of the current study was to characterize and compare the pharmacokinetics and pharmacodynamics of lorazepam and midazolam administered as continuous intravenous infusions for postoperative sedation of surgical ICU patients. Methods: With Institutional Review Board approval, 24 consenting adult surgical patients were given either lorazepam or midazolam in a double-blind fashion (together with either intravenous fentanyl or epidural morphine for analgesia) through target-controlled intravenous infusions titrated to maintain a moderate level of sedation for 12‐72 h postoperatively. Moderate sedation was defined as a Ramsay Sedation Scale score of 3 or 4. Sedation scores were measured, together with benzodiazepine plasma concentrations. Population pharmacokinetic and pharmacodynamic parameters were estimated using nonlinear mixed-effects modeling. Results: A two-compartment model best described the pharmacokinetics of both lorazepam and midazolam. The pharmacodynamic model predicted depth of sedation for both midazolam and lorazepam with 76% accuracy. The estimated sedative potency of lorazepam was twice that of midazolam. The predicted C50,ss (plasma benzodiazepine concentrations where P(Sedation > ss) 5 50%) values for midazolam (sedation score [SS] > n, where n 5 a Ramsay Sedation Score of 2, 3 ,...6 )were 68, 101, 208, 304, and 375 ng/ml. The corresponding predicted C50,ss values for lorazepam were 34, 51, 104, 152, and 188 ng/ml, respectively. Age, fentanyl administration, and the resolving effects of surgery and anesthesia were significant covariates of benzodiazepine sedation. The relative amnestic potency of lorazepam to midazolam was 4 (observed). The predicted emergence times from sedation after a 72-h benzodiazepine infusion for light (SS 5 3) and deep (SS 5 5) sedation in a typical patient were 3.6 and 14.9 h for midazolam infusions and 11.9 and 31.1 h for lorazepam infusions, respectively. Conclusions: The pharmacology of intravenous infusions of lorazepam differs significantly from that of midazolam in critically ill patients. This results in significant delays in emergence from sedation with lorazepam as compared with midazolam when administered for ICU sedation.