SummaryDexmedetomidine, a highly selective and potent a 2 -adrenergic agonist, has a potentially useful role as a sedative agent in patients requiring intensive care. As part of a larger European multicentre trial, a total of 119 postoperative cardiac and general surgical patients requiring ventilation and sedation in an intensive care unit were enrolled in four centres in the United Kingdom. One hundred and five patients were randomly allocated to receive either dexmedetomidine or placebo with rescue sedation and analgesia provided by midazolam and morphine, respectively. Compared with the control group, intubated patients receiving dexmedetomidine required 80% less midazolam [mean 4.9 (5.8) mg.kg ¹1.h ¹1 vs. 23.7 (27.5) mg.kg ¹1.h ¹1 , p < 0.0001], and 50% less morphine [11.2 (13.4) mg.kg. Cardiovascular effects and adverse events could be predicted from the known properties of alpha-2 agonists. In conclusion, dexmedetomidine is a useful agent for the provision of postoperative analgesia and sedation.

The alpha2 agonist dexmedetomidine is a new sedative and analgesic agent which is licensed in the USA for post-operative intensive care sedation. We compared dexmedetomidine with propofol in patients requiring sedation in intensive care. Twenty adult patients expected to require a minimum of 8 h artificial ventilation after surgery were randomized to receive sedation with either dexmedetomidine or propofol infusions. Additional analgesia, if required, was provided by an alfentanil infusion. Depth of sedation was monitored using both the Ramsay sedation score (RSS) and the bispectral index (BIS). Cardiovascular, respiratory, biochemical and haematological data were obtained. Patients' perceptions of their intensive care stay were assessed using the Hewitt questionnaire. Sedation was equivalent in the two groups [median (interquartile range): RSS, propofol group 5 (4-5), dexmedetomidine group 5 (4-6) (P=0.68); BIS, propofol group 53 (41-64), dexmedetomidine group 46 (36-58); P=0.32], but the propofol group received three times more alfentanil compared with patients sedated with dexmedetomidine [2.5 (2.2-2.9) mg h(-1) versus 0.8 (0.65-1.2) mg h(-1) (P=0.004)]. No differences were found in arterial pressures between the groups, but heart rate was significantly lower in the dexmedetomidine group [mean (SD) 75 (6) vs 90 (4) beats min(-1)]. Extubation times were similar and rapid with the use of both sedative agents [median (range) 28 (20-50) and 29 (15-50) min (P=0.63) respectively for the propofol and dexmedetomidine groups]. No adverse events related to the sedative infusions occurred in either group. Despite ventilation and intubation, patients sedated with dexmedetomidine could be easily roused to cooperate with procedures (e.g. physiotherapy, radiology) without showing irritation. From the clinician's and patient's perspectives, dexmedetomidine is a safe and acceptable sedative agent for those requiring intensive care. The rate pressure product is reduced in patients receiving dexmedetomidine, which may protect against myocardial ischaemia. Dexmedetomidine reduces the requirement for opioid analgesia.

Mean dexmedetomidine pharmacokinetic variables seen in postoperative, intensive care patients were similar to those previously found in volunteers, with the exception of the steady-state volume of distribution. A small loading dose provided effective sedation with no adverse events.

Sedation with dexmedetomidine is efficacious in critically ill medical patients requiring mechanical ventilation in the intensive care unit. A reduction in loading infusion is advised, but higher maintenance infusions may be required to that seen previously in the postoperative ICU patient.

We have compared the effects of dexmedetomidine and propofol on endocrine, metabolic, inflammatory and cardiovascular responses in patients in the intensive care unit (ICU) after major surgery. Twenty patients who were expected to require 8 h of post-operative sedation and ventilation were allocated randomly to receive either an infusion of dexmedetomidine 0.2-2.5 microg kg(-1) h(-1) or propofol 1-3 mg kg(-1) h(-1). Arterial pressure, heart rate and sequential concentrations of circulating cortisol, adrenocorticotrophic hormone (ACTH), growth hormone, prolactin, insulin, glucose and interleukin 6 were measured. An ACTH stimulation test was performed in all patients who received dexmedetomidine. Heart rate was significantly lower in the dexmedetomidine patients. There were no differences in arterial pressure, cortisol, ACTH, prolactin and glucose concentrations between the two groups. A positive response to the ACTH stimulation test varied depending on the diagnostic criteria used. The insulin concentration was significantly lower in the dexmedetomidine group at 2 h (P=0.021), although this did not affect blood glucose concentrations. Growth hormone concentrations were significantly higher in dexmedetomidine-treated patients overall (P=0.036), but circulating concentrations remained in the physiological range. Interleukin 6 decreased in the dexmedetomidine group. We conclude that dexmedetomidine infusion does not inhibit adrenal steroidogenesis when used for short-term sedation after surgery.

A simple validated scoring system to predict mortality in medical patients with precise 'intervention-calling scores' has been developed.

The respiratory effects of dexmedetomidine were retrospectively examined in 33 postsurgical patients involved in a randomised, placebo-controlled trial after extubation in the intensive care unit (ICU). Morphine requirements were reduced by over 50% in patients receiving dexmedetomidine. There were no differences in respiratory rates, oxygen saturations, arterial pH and arterial partial carbon dioxide tension (PaCO 2 ) between the groups. Interestingly the arterial partial oxygen tension (PaO 2 ) : fractional inspired oxygen (FIO 2 ) ratios were statistically significantly higher in the dexmedetomidine group. Dexmedetomidine provides important postsurgical analgesia and appears to have no clinically important adverse effects on respiration in the surgical patient who requires intensive care. Introduction:The α 2 -agonist dexmedetomidine is a new class of sedative drug that is being investigated for use in ICU settings. It is an effective agent for the management of sedation and analgesia after cardiac, general, orthopaedic, head and neck, oncological and vascular surgery in the ICU [1]. Cardiovascular stability was demonstrated, with significant reductions in rate-pressure product during sedation and over the extubation period. Dexmedetomidine possesses several properties that may additionally benefit those critically ill patients who require sedation. In spontaneously breathing volunteers, intravenous dexmedetomidine caused marked sedation with only mild reductions in resting ventilation at higher doses [2]. Dexmedetomidine reduces the haemodynamic response to intubation and extubation [3][4][5] and attenuates the stress response to surgery [6], as a result of the α 2 -mediated reduction in sympathetic tone. Therefore, it should be possible to continue sedation with dexmedetomidine over the stressful extubation period without concerns over respiratory depression, while ensuring that haemodynamic stability is preserved. The present study is a retrospective analysis of the respiratory response to dexmedetomidine in 33 postsurgical patients (who were involved in a randomized, double-blind, placebocontrolled trial [1]) after extubation in the ICU. Methods: Patients who participated in the present study were admitted after surgery to our general or cardiothoracic ICUs, and were expected to receive at least 6 h of postsurgical sedation and artificial ventilation. On arrival in the ICU after surgery, patients were randomized to receive either dexmedetomidine or placebo (normal saline) with rescue sedation and analgesia being provided, only if clinically needed, with midazolam and morphine boluses, respectively. Sedation was titrated to maintain a Ramsay Sedation Score [7] of 3 or greater while the patients were intubated, and infusions of http://ccforum.com/content/4/5/302 http://ccforum.com/content/4/5/302 study drug were continued for a maximum of 6 h after extubation to achieve a Ramsay Sedation Score of 2 or greater. The patients were intubated and ventilated with oxygenenriched air to attain acceptable arterial ...

ObjectiveCritically appraise prediction models for hospital-acquired acute kidney injury (HA-AKI) in general populations.DesignSystematic review.Data sourcesMedline, Embase and Web of Science until November 2016.EligibilityStudies describing development of a multivariable model for predicting HA-AKI in non-specialised adult hospital populations. Published guidance followed for data extraction reporting and appraisal.Results14 046 references were screened. Of 53 HA-AKI prediction models, 11 met inclusion criteria (general medicine and/or surgery populations, 474 478 patient episodes) and five externally validated. The most common predictors were age (n=9 models), diabetes (5), admission serum creatinine (SCr) (5), chronic kidney disease (CKD) (4), drugs (diuretics (4) and/or ACE inhibitors/angiotensin-receptor blockers (3)), bicarbonate and heart failure (4 models each). Heterogeneity was identified for outcome definition. Deficiencies in reporting included handling of predictors, missing data and sample size. Admission SCr was frequently taken to represent baseline renal function. Most models were considered at high risk of bias. Area under the receiver operating characteristic curves to predict HA-AKI ranged 0.71–0.80 in derivation (reported in 8/11 studies), 0.66–0.80 for internal validation studies (n=7) and 0.65–0.71 in five external validations. For calibration, the Hosmer-Lemeshow test or a calibration plot was provided in 4/11 derivations, 3/11 internal and 3/5 external validations. A minority of the models allow easy bedside calculation and potential electronic automation. No impact analysis studies were found.ConclusionsAKI prediction models may help address shortcomings in risk assessment; however, in general hospital populations, few have external validation. Similar predictors reflect an elderly demographic with chronic comorbidities. Reporting deficiencies mirrors prediction research more broadly, with handling of SCr (baseline function and use as a predictor) a concern. Future research should focus on validation, exploration of electronic linkage and impact analysis. The latter could combine a prediction model with AKI alerting to address prevention and early recognition of evolving AKI.