Return to Sport, Re-injury and Performance After the Anterior Cruciate Ligament Reconstruction: Evaluating the Role of International Knee Documentation Committee (IKDC) and Knee Injury and Osteoarthritis Outcome Score (KOOS) Scoring Systems.

Introduction Anterior cruciate ligament (ACL) tears are common injuries that can considerably impact an individual's quality of life and athletic performance. In these cases, surgical reconstruction of the ligament can be considered to restore stability to the knee. This study aims to investigate the time taken for individuals to return to sport post-ACL reconstruction, assess the rate of re-injury and evaluate the reliability of the International Knee Documentation Committee (IKDC) and Knee Injury and Osteoarthritis Outcome Score (KOOS) scoring systems in predicting a return to sport at the pre-injury level. Methods In this retrospective study, a total of 104 patients who underwent ACL reconstruction between January 2016 and December 2022 by one surgical team at Mater Dei Hospital, Malta were evaluated using a self-administered questionnaire. The questionnaire was based on different components including the sport practised at the time of injury, sport engagement classification, return to sport, the ability to return to pre-injury levels of performance and re-injury. The participants then had to fill in IKDC and KOOS evaluation forms. Results In this study, 73% (n=76) of individuals successfully returned to sport after ACL reconstruction, with no significant difference being found between professional and recreational athletes (Chi-squared=0.00455, p=0.95). After reconstruction, 31.7% (n=33) of participants experienced an ipsilateral or contralateral ACL tear, with those returning to sport within six months showing a fivefold increase in re-injury risk compared to individuals who returned at eight or 12 months, suggesting a significant association between return duration and re-injury. The relationship between scoring systems and return to sport at the pre-injury level of performance was analysed using binary logistic regression, revealing that achieving scores of 85.6 or higher in IKDC or 89 or higher in KOOS meant having a 95% probability of returning to sport at the pre-injury level. Conclusions By considering these scoring systems with other post-operative criteria, clinicians can offer a more customised rehabilitation plan tailored to each patient who undergoes ACL reconstruction.

Effects of clonidine and midazolam premedication on bispectral index and recovery after elective surgery.

BACKGROUND AND OBJECTIVES: Alpha-2 agonists offer useful effects that make these drugs an interesting alternative for pharmacological premedication. METHODS: In a randomized, double-blind study, effects of clonidine (150 microg orally), midazolam (7.5 mg orally) and placebo administered 60-90 min prior to estimated anaesthesia induction time were investigated in 60 healthy ASA I or II patients. All patients received dipotassiumchlorazepate the evening before surgery. At predefined time points, effects of premedication on bispectral index, sedation score and visual analogue scales for anxiety and pain, cognitive function and stress hormones were determined. RESULTS: Administration of low-dose clonidine was associated with slightly lower bispectral index scores than a standard dose of midazolam or placebo. There were no significant differences in sedation score, visual analogue scale for anxiety and pain and cognitive function between treatment regimens. Clonidine, but not midazolam, reduced anaesthetic requirements for induction of anaesthesia and prevented an increase in heart rate as well as an increase in adrenocorticotropic hormone plasma levels during the preoperative period (P < 0.05 vs. placebo). Clonidine administration did not delay postoperative recovery. CONCLUSION: Clonidine augmented haemodynamic stability and partially blunted stress responses as determined by adrenocorticotropic hormone plasma levels. In addition, clonidine did not delay postoperative recovery. Therefore, surrogate parameters indicate that preanaesthetic medication with clonidine may be superior to midazolam in healthy individuals. Further studies have to confirm these results with regard to outcome parameters.

Propofol sedation is reduced by delta9-tetrahydrocannabinol in mice.

BACKGROUND: Delta9-tetrahydrocannabinol (Delta9-THC) induces analgesic effects and alterations of alertness. It has been reported that propofol increases endocannabinoid levels in the brain, but the effects of Delta9-THC on propofol sedation remain unclear. Our aim was to characterize the interaction between Delta9-THC and propofol in terms of sedation and analgesia. METHODS: Sedation was monitored by a rota-rod and analgesia by tail-flick latencies. Twenty mice received intraperitoneal injections of 50 mg/kg Delta9-THC with 50, 75 and 100 mg/kg propofol after baseline values were established for each drug. Control experiments were performed with Delta9-THC and thiopental or Intralipid. RESULTS: Injection of 50 mg/kg propofol caused a rapid onset of sedation with a minimum of 24 s on the rota-rod. Fifty mg/kg Delta9-THC alone had no sedative effects. Administration of Delta9-THC significantly reduced the sedative effect of propofol to at least 60 s on the rota-rod (P < 0.001). After increasing the propofol dose to 100 mg/kg in the presence of Delta9-THC, sedation was re-established with 27 s on the rota-rod. Thiopental sedation was significantly reduced (P < 0.01) in the presence of Delta9-THC. CONCLUSION: The results indicate a dose-dependent antagonistic interaction between Delta9-THC and propofol, and also between Delta9-THC and thiopental.

Differential effects of alpha 2-adrenoceptors in the modulation of the thermoregulatory response in mice induced by meperidine.

BACKGROUND: Meperidine proved to be more effective in treatment of shivering than equianalgesic doses of other opioids, especially pure mu-agonists. Further, meperidine has well known nonopioid actions including agonistic effects at alpha2-adrenoceptors in vitro. Accordingly, the authors investigated nonopioid receptor-mediated effects of meperidine on thermoregulation using a mice model of nonshivering thermogenesis. To differentiate conceivable alpha2-adrenoceptor subtype specific interactions the authors analyzed wild-type mice and knock-out mice with deletion of the alpha2A-, alpha2B-, or alpha2C-adrenoceptor. METHODS: Ten mice per group (n = 60) were injected with saline, meperidine (20 mg/kg), saline plus naloxone (125 microg/kg), meperidine plus naloxone, fentanyl (50 microg/kg) plus naloxone, or meperidine plus atipamezole (2 mg/kg) intraperitoneally. Each mouse was subjected to the six different treatments. Then they were positioned into a plexiglas chamber where rectal temperature and mixed expired carbon dioxide were measured while whole body cooling was performed. Maximum response intensity and thermoregulatory threshold temperature of nonshivering thermogenesis were analyzed. RESULTS: Meperidine decreased the thermoregulatory threshold temperature in wild-type mice and alpha2B- and alpha2C-adrenoceptor knock-out mice. This effect ended after injection of the alpha2-adrenoceptor antagonist atipamezole. In wild-type and alpha2B-adrenoceptor knock-out mice, the decrease of thermoregulatory threshold was not reversible by administration of the opioid receptor antagonist naloxone. In contrast, in alpha2A-adrenoceptor knock-out mice, no decline of thermoregulatory threshold following meperidine injection was detectable. Maximum response intensity of nonshivering thermogenesis was comparable in all groups. CONCLUSIONS: The authors' results suggest a major role of alpha2-adrenoceptors, especially the alpha2A subtype, in the mediation of thermoregulatory effects caused by meperidine in mice.

Additive interaction of the cannabinoid receptor I agonist arachidonyl-2-chloroethylamide with etomidate in a sedation model in mice.

BACKGROUND: Both propofol and volatile anesthetics have been reported to interact with the endocannabinoid system. The purpose of this study was to evaluate the effect of selective agonists for cannabinoid receptor types 1 and 2 on etomidate-induced sedation. METHODS: A controlled, blinded, experimental study was performed in 20 mice that received intraperitoneal injections of etomidate, the cannabinoid1 receptor agonist arachidonyl-2-chloroethylamide (ACEA), the cannabinoid2 receptor agonist JWH 133 alone, and both ACEA and JWH 133 combined with etomidate. The cannabinoid1 receptor antagonist AM 251 and the cannabinoid2 receptor antagonist AM 630 were administered 10 min before the delivery of ACEA and JWH 133, respectively. Each drug combination was applied to 6-8 mice of these 20 study animals. Sedation was monitored by a Rota-Rod (Ugo Basile, Comerio, Italy). Isobolographic analysis was used for evaluation of pharmacologic interaction. RESULTS: Single drug administration of etomidate and ACEA produced dose- and time-dependent decreased time on the Rota-Rod (P < 0.05). No sedative effect was seen after JWH 133. Etomidate-induced sedation was significantly increased and prolonged with ACEA (P < 0.05), but not with JWH 133. Isobolographic analysis revealed an additive interaction between ACEA and etomidate that was antagonized by the cannabinoid1 receptor antagonist AM 251. The cannabinoid1 receptor antagonist had no effect on etomidate alone. CONCLUSIONS: Etomidate-induced sedation was increased and prolonged by activation of the cannabinoid1 receptor, but not of the cannabinoid2 receptor, in mice. However, this interaction was only additive.

Dexmedetomidine increases hippocampal phosphorylated extracellular signal-regulated protein kinase 1 and 2 content by an alpha 2-adrenoceptor-independent mechanism: evidence for the involvement of imidazoline I1 receptors.

BACKGROUND: Dexmedetomidine is a potent and selective alpha2-adrenoceptor (alpha2AR) agonist that exhibits a broad pattern of actions, including sedation, analgesia, and neuroprotection. Recent studies have emphasized the role of phosphorylated extracellular signal-regulated protein kinases (pERK1 and 2) in coupling rapid events such as neurotransmitter release and receptor stimulation long-lasting changes in synaptic plasticity and cell survival. Here, the authors hypothesized that dexmedetomidine increases pERK1 and 2 content and examined the mechanisms involved in this effect. METHODS: The effects of dexmedetomidine and their sensitivity to various pharmacologic agents on expression of pERK1 and 2 were studied by Western blots in hippocampal slices obtained from rats, wild-type mice, and mice carrying targeted deletions of the alpha2AR subtypes. RESULTS: Dexmedetomidine induced a concentration-related increase in the expression of pERK1 and 2 in rat hippocampal slices (EC50 [95% confidence interval] for pERK1, 0.97 [0.68-1.37] microm; for pERK2, 1.15 [0.62-2.14] microm). This effect was insensitive to the inhibitors of the alpha2AR-mediated signaling pathway, to prazosin, and to PP2, an inhibitor of the focal adhesion kinase-Src kinases. In contrast, it was still present in mice deleted for each of the alpha2AR subtypes and was markedly decreased by the antagonist of the I1-imidazoline receptors efaroxan, by phospholipase C and protein kinase C inhibitors, and by PD 098059, a direct inhibitor of ERK1 and 2 phosphorylation. CONCLUSION: Dexmedetomidine increases the expression of pERK1 and 2 via mechanisms independent of alpha2AR activation. The I1-imidazoline receptors likely contribute to these effects. The results may be relevant to some long-term effects (e.g., neuroprotective) of dexmedetomidine in the brain.

The anesthetic effects of etomidate: species-specific interaction with alpha 2-adrenoceptors.

BACKGROUND: The IV anesthetic, etomidate, has structural and clinical similarities to specific alpha2-adrenoceptor agonists such as dexmedetomidine. We investigated whether the sedative effects of etomidate may be mediated by alpha2-adrenoceptors. METHODS: The anesthetic potency of etomidate (1-20 microM) was determined in Xenopus laevis tadpoles in the absence and presence of the specific alpha2-adrenoceptor antagonist atipamezole (10 microM). Anesthesia was defined as loss of righting reflex. Nonlinear logistic regression curves were fitted to the data and half-maximal effective concentrations and the slopes of the curves were calculated. Additionally, sedative/ hypnotic effects of etomidate (8 mg/kg IP) were studied by rotarod test in wild-type (WT) mice and mice carrying targeted deletions of the alpha2A-adrenoceptor gene (alpha2A-KO). Data are presented as mean +/- sem. RESULTS: The fraction of anesthetized tadpoles increased with increasing concentrations of etomidate. Atipamezole significantly increased the half-maximal effective concentration of etomidate (4.5 +/- 0.2 microM; slope: 2.6 +/- 0.3) to 8.4 +/- 0.4 microM (slope: 2.3 +/- 0.3). Etomidate resulted in time-dependent sedative effects in all mice, as assessed by rotarod performance. In WT mice, the sedative effects of etomidate were not decreased by atipamezole (2 mg/kg). Consistently, etomidate-induced sedation was not reduced in alpha2A-KO animals compared with WT mice. CONCLUSIONS: The sedative effects of etomidate exhibit a species-specific interaction with alpha2-adrenoceptors. Although the decrease in potency of etomidate by atipamezole may be caused by an interaction with alpha2-adrenoceptors in X. laevis tadpoles, results in mice indicate that the hypnotic effect of etomidate does not require alpha2-adrenoceptors.

Monitoring consciousness in intensive care medicine.

Sedation and analgesia are important components of care for critically ill patients. Avoiding over-as well as undersedation is of utmost importance as both states carry considerable risks and may influence outcome. The management of sedation has changed dramatically over the past two decades from providing a dosage level by which the patient was kept in a deep stage of anaesthesia to a current dosing strategy allowing the administration of drugs in line with individual need, resulting in most cases in a slightly sedated, cooperative patient. The importance of monitoring the level of sedation and analgesia has only recently been realised. Most importantly, regularly determining the appropriate level of sedation and analgesia as well as monitoring the desired level of sedation will help to minimise the adverse effects of sedation. Clinical sedation scales are, however, subjective, and most lack proper validation. Thus, an objective measure of sedation, such as the use of processed electroencephalogram (EEG) parameters is desirable. Processed EEG algorithms such as the bispectral index were initially introduced into clinical practice as a tool to assess the depth of anaesthesia objectively in the operating room. However, patients under general anaesthesia differ from those in an intensive care unit. Accordingly, most results from studies evaluating the performance of processed EEG parameters in critically ill patients have not been satisfactory. At present, monitoring sedation with processed EEG parameters cannot generally be recommended. However, in special situations such as deep sedation and neuromuscular blockade, in which clinical sedation scales are prone to failure, the bispectral index may help to assess the level of sedation.

The effects of dexmedetomidine on perinatal excitotoxic brain injury are mediated by the alpha2A-adrenoceptor subtype.

We performed the current study in mice lacking individual alpha2-adrenoceptor subtypes to elucidate the contribution of alpha(2)-adrenoceptor subtypes to the neuroprotective properties of dexmedetomidine in a model of perinatal excitotoxic brain injury. On postnatal Day 5, wild-type mice and mice lacking alpha2A-adrenoceptor (alpha2A-KO) or alpha2C-adrenoceptor subtypes (alpha2C-KO) were randomly assigned to receive dexmedetomidine (3 microg/kg) or phosphate-buffered saline intraperitoneally. Thirty minutes after the intraperitoneal injection, the glutamatergic agonist ibotenate (10 microg) was intracerebrally injected, producing transcortical necrosis and white matter lesions that mimic perinatal human hypoxic-like lesions. Quantification of the lesions was performed on postnatal Day 10 by histopathologic examination. Dexmedetomidine reduced mean lesion size in the cortex of wild-type mice and alpha2C-KO mice by 44% and 49%, respectively. Ibotenate-induced white matter lesions were reduced by 71% (wild-type mice) and 75% (alpha2C-KO mice) after pretreatment with dexmedetomidine. In contrast, in alpha2A-KO mice, dexmedetomidine did not protect against the cortical excitotoxic insult, and white matter lesions were even more pronounced (82% increase of mean lesion size). Dexmedetomidine provides potent neuroprotection in a model of perinatal excitotoxic brain damage. This effect was completely abolished in alpha2A-KO mice, suggesting that the neuroprotective effect is mediated via the alpha2A-adrenoceptor subtype.

Neuroendocrine stress response and heart rate variability: a comparison of total intravenous versus balanced anesthesia.

Attenuating intraoperative stress is a key factor in improving outcome. We compared neuroendocrine changes and heart rate variability (HRV) during balanced anesthesia (BAL) versus total IV anesthesia (TIVA). Forty-three patients randomly received either BAL (sevoflurane/remifentanil) or TIVA (propofol/remifentanil). Depth of anesthesia was monitored by bispectral index. Stress hormones were measured at 7 time points (P1 = baseline; P2 = tracheal intubation; P3 = skin incision; P4 = maximum operative trauma; P5 = end of surgery; P6 = tracheal extubation; P7 = 15 min after tracheal extubation). HRV was analyzed by power spectrum analysis: very low frequency (VLF), low frequency (LF), high frequency (HF), LF/HF ratio, and total power (TP). LF/HF was higher in TIVA at P6 and TP was higher in TIVA at P3-7 (P3: 412.6 versus 94.2; P4: 266.7 versus 114.6; P5: 290.3 versus 111.9; P6: 1523.7 versus 658.1; P7: 1225.6 versus 342.6 ms2)). BAL showed higher levels of epinephrine (P7: 100.5 versus 54 pg/mL), norepinephrine (P3: 221 versus 119.5; P4: 194 versus 130.5 pg/mL), adrenocorticotropic hormone (P2 10.5 versus 7.7; P5: 5.3 versus 3.6; P6: 10.9 versus 5.3; P7: 20.5 versus 7.1 pg/mL) and cortisol (P7: 6.9 versus 3.9 microg/dL). This indicates a higher sympathetic outflow using BAL versus TIVA during ear-nose-throat surgery.

Comparison of two bispectral index algorithms in monitoring sedation in postoperative intensive care patients.

OBJECTIVE: Comparison of two versions of bispectral index (BIS) derived from the electroencephalogram in mechanically ventilated and continuously sedated patients after major abdominal surgery. DESIGN: Prospective, cohort, observational, unblinded study. SETTING: Surgical intensive care unit of a university hospital. PATIENTS: Forty-six patients undergoing major abdominal surgery scheduled for postoperative mechanical ventilation and continuous sedation. INTERVENTIONS: Patients were continuously sedated using propofol and sufentanil. MEASUREMENTS AND MAIN RESULTS: Electrodes for determination of BIS were placed at the forehead of the patients according to the manufacturer's specifications immediately after arrival to the intensive care unit. The level of consciousness was assessed every 2 hrs by a clinical sedation scale (Ramsay sedation scale, levels 1-6). BIS, electromyographic activity, and signal quality index were recorded simultaneously at the same time as the Ramsay scale for 24 hrs or until patients were ready for extubation. BIS (version 2.10) and BIS XP (version 3.12) were determined at 2-hr intervals. BIS and BIS XP showed a high correlation of readings (rs = .79, p < .01). However, the methods did not yield identical results. Both variables were significantly influenced by electromyographic activity, especially at high values, whereas there was only a weak correlation with body temperature. Some of the deeply sedated patients (Ramsay 5 or 6) had BIS readings >80 (BIS, 16%; BIS XP, 13%; p = not significant). CONCLUSIONS: The newer algorithm BIS XP did not perform better than the previous version BIS in patients after major surgery who were mechanically ventilated and sedated on an intensive care unit. This precludes the use of BIS or BIS XP for distinguishing, among deeply sedated ICU patients, those with and without preserved cerebral electrical activity.

Sevoflurane but not propofol preserves myocardial function during minimally invasive direct coronary artery bypass surgery.

Volatile anesthetics exert cardioprotective properties in experimental and clinical studies. We designed this study to investigate the effects of sevoflurane on left ventricular (LV) performance during minimally invasive direct coronary artery bypass grafting (MIDCAB) without cardiopulmonary bypass. Fifty-two patients scheduled for MIDCAB surgery were randomly assigned to a propofol or a sevoflurane group. Apart from the anesthetics used, there was no difference in surgical and anesthetic management. After determination of cardiac troponin T, creatine kinase, and creatine kinase MB, electrocardiographic (ECG) data and echocardiography variables (myocardial performance index and early to atrial filling velocity ratio) the left anterior descending coronary artery (LAD) was clamped until anastomosis with the left internal mammary artery was completed. During LAD occlusion and during reperfusion, echocardiography measurements were repeated. Blood samples were obtained repeatedly for up to 72 h. After LAD occlusion, myocardial performance index and early to atrial filling velocity ratio in the propofol group deteriorated significantly from 0.40 +/- 0.12 and 1.29 +/- 0.35 to 0.49 +/- 0.10 and 1.13 +/- 0.22, respectively, whereas there was no change in the sevoflurane group. In the propofol group myocardial performance index remained increased (0.47 +/- 0.11) compared with baseline during reperfusion. There were no significant differences in ECG and laboratory values between groups. In conclusion, during a brief period of ischemia in patients undergoing MIDCAB surgery, sevoflurane preserved myocardial function better than propofol.

Dexmedetomidine in anaesthesia.

PURPOSE OF REVIEW: The development of dexmedetomidine, a potent and highly selective alpha2-adrenoceptor agonist, has created new interest in the use of alpha2-adrenoceptor agonists, and has led to its evaluation in various yet non-approved perioperative settings. The current review focuses on the usefulness of dexmedetomidine in anaesthesia practice. RECENT FINDINGS: Recently acquired knowledge and experience with dexmedetomidine in perioperative use will be presented and discussed in the context of known pharmacological properties. SUMMARY: Dexmedetomidine offers beneficial pharmacological properties, providing dose-dependent sedation, analgesia, sympatholysis and anxiolysis without relevant respiratory depression. The side-effects are predictable from the pharmacological profile of (2-adrenoceptor agonists. In particular, the unique sedative properties of dexmedetomidine resulted in several interesting applications in anaesthesia practice, promising benefits in the perioperative use of this compound. However, dexmedetomidine was approved for sedation in the intensive care unit in the USA in 1999, and administration in anaesthesia practice remains an 'off-label' use. Further studies are needed to establish the role of dexmedetomidine in the perioperative period.

The effect of meperidine on thermoregulation in mice: involvement of alpha2-adrenoceptors.

Meperidine has potent antishivering properties. The underlying mechanisms are not fully elucidated, but recent investigations suggest that alpha2-adrenoceptors are likely to be involved. We performed the current study to investigate the effects of meperidine on nonshivering thermogenesis in a model of thermoregulation in mice. After injection (0.1 mL/kg intraperitoneally) of saline, meperidine (20 mg/kg), the specific alpha2-adrenoceptor antagonist atipamezole (2 mg/kg), plus saline or atipamezole plus meperidine, respectively, mice were positioned in a Plexiglas chamber. Rectal temperature and mixed expired carbon dioxide were measured after provoking thermoregulatory effects by whole body cooling. Maximum response intensity of nonshivering thermogenesis and the thermoregulatory threshold for nonshivering thermogenesis, which was defined as the temperature at which a sustained increase in expiratory carbon dioxide can be measured, were investigated. Meperidine significantly decreased the threshold of nonshivering thermogenesis (36.6 degrees C +/- 0.7 degrees C) versus saline (37.9 degrees C +/- 0.6 degrees C) and versus atipamezole plus saline (37.8 degrees C +/- 0.4 degrees C; P <0.01). This effect was abolished after administration of meperidine combined with atipamezole (37.7 degrees C +/- 0.6 degrees C; P <0.05). Meperidine did not decrease the maximum intensity of nonshivering thermogenesis. The results suggest a major role of alpha2-adrenoceptors in the inhibition of thermoregulation by meperidine in mice.

Comparison of esophageal Doppler, pulse contour analysis, and real-time pulmonary artery thermodilution for the continuous measurement of cardiac output.

OBJECTIVE: Continuous measurement of cardiac output (CCO) is of great importance in the critically ill. However, pulmonary artery thermodilution has been questioned for possible complications associated with right heart catheterization. Furthermore, measurements are delayed in the continuous mode during rapid hemodynamic changes. A new pulmonary artery catheter CCO device (Aortech, Bellshill, Scotland) enabling real-time update of cardiac output was compared with 2 different, less-invasive methods of CCO determination, esophageal Doppler and pulse contour analysis. DESIGN: Prospective, observational study. SETTING: University hospital, single institution. PARTICIPANTS: Patients scheduled for elective coronary artery bypass grafting (CABG). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: CCO measurements were analyzed using a Bland-Altman plot. Bias between CCO and pulse contour cardiac output (PCCO), and Doppler-derived cardiac output (UCCO) was (mean +/- 1 SD) -0.71 +/- 1 L/min versus -0.15 +/- 1.09 L/min, and between UCCO and PCCO -0.58 +/- 1.06 L/min. Bias was not significantly different among methods, nor were comparative values before and after cardiopulmonary bypass (p > 0.05). CONCLUSIONS: Agreement between the CCO method and both less-invasive measurements was clinically acceptable. There were no adverse events associated with the use of either device.

Activation of alpha 2B-adrenoceptors mediates the cardiovascular effects of etomidate.

BACKGROUND: The intravenous anesthetic etomidate exhibits structural similarities to specific alpha2-adrenoceptor agonists of the type such as dexmedetomidine. The current study was performed to elucidate the possible interaction of etomidate with alpha2-adrenoceptors in mice lacking individual alpha2-adrenoceptor subtypes (alpha2-KO). METHODS: Sedative and cardiovascular responses to etomidate and the alpha2-agonist, dexmedetomidine, were determined in mice deficient in alpha2-receptor subtypes. Inhibition of binding of the alpha2-receptor antagonist [3H]RX821002 to recombinant alpha2-receptors by etomidate was tested in human embryonic kidney (HEK293) cells in vitro. RESULTS: In vivo, loss and recovery of the righting reflex required similar times after intraperitoneal injection of etomidate in wild-type and in alpha2A-receptor-deficient mice, indicating that the hypnotic effect of etomidate in mice does not require the alpha2A-receptor subtype. Intravenous injection of etomidate resulted in a transient increase (duration 2.4 +/- 0.2 min) in arterial blood pressure in wild-type mice (17 +/- 3 mmHg). Etomidate did not affect blood pressure in alpha2B-KO or alpha2AB-KO mice. In membranes from HEK293 cells transfected with alpha2-receptors, etomidate inhibited binding of the alpha2-antagonist, [3H]RX821002, with higher potency from alpha2B- and alpha2C-receptors than from alpha2A-receptors (Ki alpha2A 208 microm, alpha2B 26 microm, alpha2C 56 microm). In alpha2B-receptor-expressing HEK293 cells, etomidate rapidly increased phosphorylation of the extracellular signal-related kinases ERK1/2. CONCLUSIONS: These results indicate that etomidate acts as an agonist at alpha2-adrenoceptors, which appears in vivo primarily as an alpha2B-receptor-mediated increase in blood pressure. This effect of etomidate may contribute to the cardiovascular stability of patients after induction of anesthesia with etomidate.

Sedation and analgesia in the intensive care unit.

PURPOSE OF REVIEW: Sedation and analgesia are important means of providing care for the critically ill patient. RECENT FINDINGS: It is now clear that posttraumatic stress disorders resulting from an intensive care unit stay may be prevented by the right level of sedation. New drug developments but also recent findings in new ventilation strategies allow for a sedation management that is better tailored to an individual's need. Most importantly, regular definition of the appropriate level of sedation and analgesia as well as monitoring of the desired level will help to avoid over- and undersedation and may ultimately improve the outcome of the patient and reduce costs. SUMMARY: Sedation and analgesia are now regarded as an integral part of treatment on the intensive care unit instead of being an unpleasant but necessary and minor issue. The importance of monitoring the level of sedation and analgesia has only recently been realized. It remains to be shown that new management strategies including an evaluation of the patient, planned interventions and the choice of drugs will further improve the care for the critically ill.