Acute kidney injury associated with endurance events-is it a cause for concern? A systematic review.

INTRODUCTION: A growing body of evidence suggests even small rises in serum creatinine (SCr) are of considerable clinical relevance. Given that participants in endurance events are exposed to potential (repeated) renal insults, a systematic review was undertaken to collate current evidence for acute kidney injury (AKI), complicating such events. METHODS: A systematic review of studies and case reports meeting inclusion criteria on Medline and EMBASE (inception to October 2015). Included: studies with markers of renal function before and after endurance or ultraendurance events; case reports of severe AKI. Two reviewers assessed risk of bias using the Newcastle-Ottawa scale. RESULTS: Eleven case report publications (n=27 individuals) of severe AKI, were retrieved, with risk factors including systemic illness or nephrotoxic medications usually identified. From 30 studies of endurance and ultraendurance events, mean rise in SCr was 29 (±12.3) µmol/L after marathon or ultramarathon (17 studies, n=568 participants) events. Where follow-up tests were conducted, SCr returned to baseline within 48 hours. Rises in biomarkers suggest potential parenchymal insult, rather than simply muscle breakdown. However, evidence of long-term deleterious effects is lacking. CONCLUSIONS: Raised levels of SCr are reported immediately after endurance events. It is not clear whether this is either clinically significant, or if repeated participation predisposes to long-term sequelae. The aetiology of severe exercise-associated AKI is usually multifactorial, with risk factors generally identified in the rare cases reported. On-site biochemistry, urine analysis and biomarkers of AKI may help identify collapsed runners who are at significant short-term risk and allow suitable follow-up.

Identifying the sick: can biochemical measurements be used to aid decision making on presentation to the accident and emergency department.

BACKGROUND: Early and accurate identification of patients who may benefit from aggressive optimal medical intervention is essential if improved outcomes in terms of survival are to be achieved. We studied the usefulness of routine clinical measurements and/or markers of metabolic abnormality in the early identification of those patients at greatest risk of deterioration on presentation to the accident and emergency department. METHODS: We conducted a prospective observational study in the accident and emergency department of a 602-bed district general hospital. Routine clinical measurements (heart rate, systolic blood pressure, temperature, oxygen saturation in room air, level of consciousness and ventilatory frequency) and venous blood analysis for metabolic markers (pH, bicarbonate, standard base excess, lactate, anion gap, strong ion difference, and strong ion gap) and biochemical markers (Na+, K+, Ca2+, Cl-, PO4- albumin, urea and creatinine) were recorded from unselected consecutive hospital admissions over two 3-month periods (September-November 2002 and February-April 2003). RESULTS: Logistic regression analysis showed that neither conventional clinical measurements upon presentation to the accident and emergency department nor venous biochemical and metabolic indices have good discriminatory ability when used as single predictors of either hospital mortality or length of hospital stay. Selecting variables from all the clinical and venous blood measurements gave a parsimonious model containing only age, heart rate, phosphate and albumin (area under the receiver operating characteristic curve, 0.82 [95% CI 0.76, 0.87]). CONCLUSIONS: A combination of clinical and venous biochemical measurements in the accident and emergency department proved the best predictors of hospital mortality. Consequently, they may be helpful as a triage tool in the accident and emergency department to help identify patients at risk of deterioration.

Perioperative fluid volume optimization following proximal femoral fracture.

BACKGROUND: Proximal Femoral Fracture (PFF) or 'hip fracture' is a frequent injury, and adverse outcomes are common. Several factors suggest the importance of developing techniques to optimize intravascular fluid volume. These may include protocols that enhance the efficacy of clinicians' assessments, invasive techniques such as oesophageal Doppler or central venous pressure monitoring, or advanced non-invasive techniques such as plethysmographic pulse volume determination. OBJECTIVES: To determine the optimal method of fluid volume optimization for adult patients undergoing surgical repair of PFF. Comparisons of fluid types, of blood transfusion strategies or of pharmacological interventions are not considered in this review. SEARCH STRATEGY: We searched CENTRAL (The Cochrane Library, issue 4, 2003), MEDLINE (1985 to 2003), EMBASE (1985 to 2003), and bibliographies of retrieved articles. Relevant journals and conference proceedings were handsearched. SELECTION CRITERIA: Randomized controlled studies comparing a fluid optimization intervention with normal practice or with another fluid optimization intervention, in patients following PFF undergoing surgery of any type under anaesthesia of any type. DATA COLLECTION AND ANALYSIS: Searches and exclusion of clearly irrelevant articles were performed by one reviewer. Two reviewers examined independently the remaining studies, extracting study quality and results data. A wide range of short- and long-term outcome data were sought. Studies were excluded if they did not meet selection criteria or if results were likely to be biased. Due to inconsistent data reporting, combination of data was not generally possible. MAIN RESULTS: Searches identified four trials, of which two studies, randomizing a total of 130 patients, were of adequate quality and addressed the review question. Both studies were of invasive advanced haemodynamic monitoring, either oesophageal Doppler ultrasonography or central venous pressure monitoring, during the intraoperative period only. In both, invasive monitoring led to significant increases in fluid volumes infused and reductions in length of hospital stay. The pooled Peto odds ratio for in-hospital fatality was 1.44 (95% confidence interval 0.45-4.62). Neither study followed patients beyond hospital discharge or assessed functional outcomes. No serious complications were directly attributable to the interventions. There were no studies of protocol-guided fluid optimization or of advanced non-invasive techniques. REVIEWER'S CONCLUSIONS: Invasive methods of fluid optimization during surgery may shorten hospital stay, but their effects on other important, patient-centred, longer-term outcomes are uncertain. Adverse effects on fatality cannot be excluded. Other fluid optimization techniques have not been evaluated. The lack of randomized studies of adequate quality addressing this important question is disappointing. More research is needed.

Pharmacokinetics of dexmedetomidine infusions for sedation of postoperative patients requiring intensive caret.

BACKGROUND: The pharmacokinetics of the alpha-2 adrenoceptor agonist dexmedetomidine were studied in 10 patients requiring postoperative sedation and mechanical ventilation in the intensive care unit (ICU), and compared with previous volunteer data. METHODS: On arrival in the ICU, sedation with dexmedetomidine was commenced with a loading dose of 2.5 microg kg(-1) h(-1) over 10 min followed by a maintenance infusion of 0.7 microg kg(-1) h(-1) into a central vein. Blood samples for measurement of plasma dexmedetomidine concentrations were taken during and after sedative infusions at predetermined intervals. Pharmacokinetic variables were estimated using non-compartmental methods. In addition, non-linear mixed effects modelling was used to obtain variable estimates not readily attainable from non-compartmental methods. Respiratory and haemodynamic data were recorded to enable correlation of any adverse events with the calculated pharmacokinetic profile. RESULTS: The harmonic mean distribution half-life of dexmedetomidine was 8.6 min and the harmonic mean terminal half-life was 3.14 h. Steady-state volume of distribution averaged 173 litres, clearance averaged 48.3 litres h(-1), and the mean residence time averaged 3.86 h. CONCLUSIONS: 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.

Effects of dexmedetomidine on adrenocortical function, and the cardiovascular, endocrine and inflammatory responses in post-operative patients needing sedation in the intensive care unit.

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.

Comparison between dexmedetomidine and propofol for sedation in the intensive care unit: patient and clinician perceptions.

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.

Respiratory effects of dexmedetomidine in the surgical patient requiring intensive care.

STATEMENT OF FINDINGS: 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 (PaCO2) between the groups. Interestingly the arterial partial oxygen tension (PaO2) : fractional inspired oxygen (FIO2) 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.

Preliminary UK experience of dexmedetomidine, a novel agent for postoperative sedation in the intensive care unit.

Dexmedetomidine, a highly selective and potent alpha2-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) microg.kg-1.h-1 vs. 23.7 (27.5) microg.kg-1.h-1, p < 0.0001], and 50% less morphine [11.2 (13.4) microg.kg-1.h-1 vs. 21.5 (19.4) microg.kg-1.h-1,p = 0.0006]. 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.