Rm Grounds

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

Dexmedetomidine, a highly selective and potent α2‐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) μg.kg−1.h−1 vs. 23.7 (27.5) μg.kg−1.h−1, p < 0.0001], and 50% less morphine [11.2 (13.4) μg.kg−1.h−1 vs. 21.5 (19.4) μg.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.

The strong ion gap does not have prognostic value in critically ill patients in a mixed medical/surgical adult ICU

AbstractObjective. To examine whether the strong ion gap (SIG) or standard base excess corrected for abnormalities of serum chloride and albumin (BEUA) can predict outcome and to compare the prognostic abilities of these variables with standard base excess (SBE), anion gap (AG), pH, and lactate, the more traditional markers of acid-base disturbance. Design. Prospective, observational study. Setting. University teaching hospital, general adult ICU. Patients. One hundred consecutive patients on admission to the ICU. Measurements and results. The anion gap (AG) was calculated and corrected for abnormal serum albumin (AGcorrected). Serum lactate was measured and SBE, BEUA, SIG, and APACHE II scores calculated for each patient. 28-day survival was recorded. There was a significant difference between the mean APACHE II (P<0.001), SBE (P<0.001), lactate (P=0.008), AG (P=0.007), pH (P<0.001), and BEUA (P=0.009) of survivors and non-survivors. There was no significant difference between the mean SIG (P=0.088), SIDeff (P=0.025), and SID app (P=0.254) between survivors and non-survivors. The pH and SBE demonstrated the best ability of the acid-base variables to predict outcome (AUROC curves 0.72 and 0.71, respectively). Neither of these were as good as the APACHE II score (AUROC 0.76) Conclusion. Traditional indices of SBE, BEUA, lactate, pH, AG, and APACHE II all discriminated well between survivors and non-survivors. In this group of patients the SIG, SIDeff, and SIGapp appear to offer no advantage in prediction of outcome and their use as prognostic markers can therefore not be advocated.

Cardiac complications associated with goal-directed therapy in high-risk surgical patients: a meta-analysis

Patients with limited cardiopulmonary reserve are at risk of mortality and morbidity after major surgery. Augmentation of oxygen delivery index (DO2I) with i.v. fluids and inotropes (goal-directed therapy, GDT) has been shown to reduce postoperative mortality and morbidity in high-risk patients. Concerns regarding cardiac complications associated with fluid challenges and inotropes may prevent clinicians from performing GDT in patients who need it most. We hypothesized that GDT is not associated with an increased risk of cardiac complications in high-risk, non-cardiac surgical patients. We performed a systematic search of Medline, Embase, and CENTRAL databases for randomized controlled trials (RCTs) of GDT in high-risk surgical patients. Studies including cardiac surgery, trauma, and paediatric surgery were excluded. We reviewed the rates of all cardiac complications, arrhythmias, myocardial ischaemia, and acute pulmonary oedema. Meta-analyses were performed using RevMan software. Data are presented as odds ratios (ORs), [95% confidence intervals (CIs)], and P-values. Twenty-two RCTs including 2129 patients reported cardiac complications. GDT was associated with a reduction in total cardiovascular (CVS) complications [OR=0.54, (0.38-0.76), P=0.0005] and arrhythmias [OR=0.54, (0.35-0.85), P=0.007]. GDT was not associated with an increase in acute pulmonary oedema [OR=0.69, (0.43-1.10), P=0.12] or myocardial ischaemia [OR=0.70, (0.38-1.28), P=0.25]. Subgroup analysis revealed the benefit is most pronounced in patients receiving fluid and inotrope therapy to achieve a supranormal DO2I, with the use of minimally invasive cardiac output monitors. Treatment of high-risk surgical patients GDT is not associated with an increased risk of cardiac complications; GDT with fluids and inotropes to optimize DO2I during early GDT reduces postoperative CVS complications.

A cost analysis of a treatment policy of a deliberate perioperative increase in oxygen delivery in high risk surgical patients

Objective:To investigate the cost implications of a treatment policy of a deliberate perioperative increase of oxygen delivery in high risk surgical patients.Design:A cost-effectiveness analysis comparing ‘protocol’ high risk surgical patients in whom oxygen delivery was specifically targeted towards 600 ml/min/m2 with ‘control’ patients.Interventions:In a randomised, controlled clinical trial we previously demonstrated a significant reduction in mortality (5.7% vs 22.2%, p=0.015) and morbidity (0.68±0.16 complications vs 1.35±0.20, p=0.008) in ‘protocol’ high risk surgical patients in whom oxygen delivery was specifically targeted towards 600 ml/min per m2 compared with ‘control’ patients. This current study retrospectively analysed the medical care and National Health Service resource use of each patient in the trial. Departmental purchasing records and business managers were consulted to identify M28.9nthe unit cost of these resources, and thereby the cost of treating each patient was calculated.Results:The median cost of treating a protocol patient was lower than for a control patient (£6,525 vs £7,784) and this reduction was due mainly to a decrease in the cost of treating postoperative complications (median £213 vs £668). The cost of obtaining a survivor was 31% lower in the protocol group.Conclusion:Perioperative increase of oxygen delivery in high risk surgical patients not only improves survival, but also provides an actual and relative cost saving. This may have important implications for the management of these patients and the funding of intensive care.

Follicular fluid levels of midazolam, fentanyl, and alfentanil during transvaginal oocyte retrieval.

OBJECTIVE To investigate the time course of changes in follicular fluid (FF) concentrations of midazolam (Roche Products Ltd., Welwyn Garden City, United Kingdom), fentanyl (Janssen Pharmaceuticals Ltd., Wantage, United Kingdom), and alfentanil (Janssen Pharmaceuticals Ltd.) during ultrasound-guided transvaginal oocyte collection. STUDY DESIGN Forty-five patients with tubal infertility were randomized to receive a bolus IV dose of midazolam, fentanyl, or alfentanil for sedation during ultrasound-guided transvaginal oocyte collection. Paracervical block with lignocaine was given for analgesia. Simultaneous blood and FF samples were drawn at 5-minute intervals after the bolus dose for analysis of drug levels. RESULTS Data were obtained on 15 women receiving midazolam and fentanyl and on 13 women receiving alfentanil. Plasma levels of all agents rose to a peak and then fell in an exponential fashion as was expected. The FF levels of the agents continued to rise significantly to 25 minutes after the bolus dose, although the absolute level was low when compared with the blood level. There were no significant differences in fertilization or pregnancy rates in the three groups, but patient numbers were small. CONCLUSION We conclude that midazolam, fentanyl, and alfentanil are found in FF after a single IV dose, but further investigation needs to be undertaken to investigate any potential influence on fertilization and implantation rates.

Outcomes of critically ill patients with cirrhosis admitted to intensive care: an important perspective from the non-transplant setting.

Aliment Pharmacol Ther 2010; 32: 233–243

Sevoflurane anaesthesia for major intra-abdominal surgery.

The cardiovascular effects and recovery characteristics of sevoflurane and isoflurane anaesthesia were compared in 30 gynaecological and 20 general surgical patients undergoing elective intra‐abdominal surgery. Patients were randomly allocated to receive either sevofurane or isofurane as the volatile agent, in a balanced anaesthetic technique including morphine and atropine prernedication and thiopentone, fentanyl. vecuronium and nitrous oxide. The concentration of volatile agent was titrated according to clinical variables. Mean heart rate, systolic and diastolic arterial pressure and duration of surgery did not differ between the two groups. Time to emergence from anaesthesia in the gynaecological patients was significantly faster after sevoflurane compared with isoflurane (p < 0.005). Sevoflurane provided stable anaesthesia during major intra‐abdominal surgery.

Routine blood-gas analysis and gastric tonometry: a reappraisal

1for whom low pHi is a sensitive predictor of poor outcome. 2 We have previously shown that in patients with systemic acidosis, pHi is closely correlated with data that can be obtained from routine blood gas analysis. 3 These findings were not unexpected, as the equations for the derivation of arterial pH and pHi contained the same variable (arterial bicarbonate concentration). In order to get around the problems of use of this monitor in the presence of acidaemia, it is now suggested that the gap between the gastric intramucosal and arterial carbon dioxide tensions ([Pr-Pa] CO2) would be a better estimate of mesenteric ischaemia. 4 Here we reanalyse our original data in order to assess whether information gained from this (Pr-Pa) CO 2 gap is correlated to acid/base variables. Full details of our methods were published previously. 3 20 consecutive critically ill patients who, by our normal criteria, were judged to need pulmonary artery catheterisation as part of their clinical management, were recruited into the study. Measurement sets consisted of tonometry measurement of PrCO 2 , selected gas analysis of arterial and mixed venous blood, measurement of whole blood lactate, cardiorespiratory variables, and calculation of pHi from standard formulae. The tonometer used was a Trip TGS catheter (Tonometrics Inc, Maryland USA), the silicone balloon being filled with 2·5 mL 0·9% saline and 60 min allowed for equilibration. The blood gas analyser (IL 1312 Blood Gas Manager, Instrumentation Laboratory, Levington, USA) underwent quality control testing daily. Correlation coefficients between the (Pr-Pa) CO 2 gap and other variables were calculated within the subject, using multiple regression with subject as a class variable. The coefficient being calculated from the sum of the squares for the (Pr-Pa) CO2 gap and residual, the sign being found from the sign of the regression coefficient for the (Pr-Pa) CO 2 gap. Important relations were taken as r>0·6 and p<0·001. In the critically ill patients studied, the (Pr-Pa) CO 2 gap correlated with pHi (r =0·71, p<0·0001) but there was no correlation between the (Pr-Pa) CO 2 gap and acid/base data derived from routine blood gas analysis, or any of the haemodynamic parameters measured. This is in contrast to the pHi, which is strongly correlated with acid/base measurements. This (Pr-Pa) CO2 gap is clearly measuring something pertinent to the splanchnic beds, but it remains to be confirmed whether it gives an indication of the effectiveness of the mesenteric circulation, and whether treatment can both reduce the gap and improve patient survival.

A prospective study into the use of NT-proBNP measurements in critically ill patients

Objective: B-type natriuretic peptide (BNP) has been shown to be a sensitive marker of cardiac dysfunction and to increase in patients with septic shock. This study seeks to confirm these findings in a mixed group of critically ill patients.Design and setting: Prospective observational study in a general intensive care unit (ITU) of a university hospital.Patients and participants: Ninety-three consecutive admissions to the general ITU.Interventions: Measurement of NT-proBNP on admission and then daily thereafter. Collection of clinical and demographical data in relation to NT-proBNP over a period of 5 days and outcome data at 28 days and hospital discharge.Measurements and results: NT-proBNP levels were raised for the whole population at each time point. NT-proBNP levels were higher in non-survivors than in survivors from ITU (p=0.02), at 28 days (p=0.02) or hospital discharge (p=0.0004). NT-proBNP was raised in patients with sepsis (11 688 (6140–20 434) vs. 767 (472–2267) ng/L, p=<0.0001), cardiac dysfun...

Tracheal dilatation complicating prolonged tracheal intubation

A patient with severe acute respiratory distress syndrome requiring prolonged tracheal intubation and mechanical ventilation is described. Tracheal dilatation was noted to have occurred following an elective surgical tracheostomy. Eventually, the patient was successfully weaned from mechanical ventilation and the tracheostomy tube removed.