Critically ill patients exhibit a range of organ dysfunctions and often require treatment with a variety of drugs including sedatives, analgesics, neuromuscular blockers, antimicrobials, inotropes and gastric acid suppressants. Understanding how organ dysfunction can alter the pharmacokinetics of drugs is a vital aspect of therapy in this patient group. Many drugs will need to be given intravenously because of gastrointestinal failure. For those occasions on which the oral route is possible, bioavailability may be altered by hypomotility, changes in gastrointestinal pH and enteral feeding. Hepatic and renal dysfunction are the primary determinants of drug clearance, and hence of steady-state drug concentrations, and of efficacy and toxicity in the individual patient. Oxidative metabolism is the main clearance mechanism for many drugs and there is increasing recognition of the importance of decreased activity of the hepatic cytochrome P450 system in critically ill patients. Renal failure is equally important with both filtration and secretion clearance mechanisms being required for the removal of parent drugs and their active metabolites. Changes in the steady-state volume of distribution are often secondary to renal failure and may lower the effective drug concentrations in the body. Failure of the central nervous system, muscle, the endothelial system and endocrine system may also affect the pharmacokinetics of specific drugs. Time-dependency of alterations in pharmacokinetic parameters is well documented for some drugs. Understanding the underlying pathophysiology in the critically ill and applying pharmacokinetic principles in selection of drug and dose regimen is, therefore, crucial to optimising the pharmacodynamic response and outcome.

A study was conducted to determine if continuous subcutaneous glucose monitoring (from MiniMed CGMS) could be used in real-time to control blood sugar level (BSL) in patients with critical illness. A closed-loop control system was constructed to use CGMS in a real-time manner, coupled with a proportional integral (PI) control algorithm based on a sliding scale approach, for automatic intravenous infusion of insulin to patients. A total of five subjects with high BSL (> 10 mmol/L) participated in formal studies of the closed-loop control system. Subjects were recruited from critically ill patients in the intensive care unit (ICU) after informed consent was obtained. Error grid analysis showed that 64.6% of the BSL readings as determined in real time using CGMS sensor, when compared to conventional BSL measurements on blood drawn from an arterial line, was clinically accurate (i.e., < 20% deviation from glucometer value). In the five patients who underwent closed-loop control, the controller managed to control only one patient's glycaemia without any manual intervention. Manual intervention was required due to the real-time sensor reading deviating more than 20% from the glucometer value, and also as a safety mechanism. Test on equality of mean and variance for BSL attained prior to, during, and post trial showed that the controller's performance was comparable to manual control. We conclude that the automatic sliding scale approach of closed-loop BSL control is feasible in patients in intensive care. More work is needed in the refinement of the algorithm and the improvement of real-time sensor accuracy.

The Non-invasive Cardiac Output (NICO) monitor (Novametrix Medical Systems Inc., Wallingford, CT, U.S.A.) utilizes a minimally-invasive partial rebreathing method to determine cardiac output by means of a differential form of the Fick equation. We evaluated the NICO monitor by comparing its output to paired measurements obtained by the standard thermodilution (TD) technique in patients who had recently undergone cardiac surgery. Forty-two paired measurements were carried out in 12 patients. The correlation between the two methods was moderate with a correlation coefficient of 0.691. Repeated measures ANOVA showed that TD measures of cardiac output were significantly higher than those obtained by the NICO monitor (P=0.0003). Comparison of the two techniques using the method described by Bland and Altman showed decreased correlation at higher values of cardiac output. We conclude that the NICO monitor may well have a place in intensive care monitoring, provided patients are not breathing spontaneously and are able to tolerate a 4 mmHg rise in P a CO 2. It is less suitable for use in patients with a high cardiac output state.

Two case reports are presented where inhaled aerosolized prostacyclin (IAP) was used to good effect as a selective pulmonary vasodilator. It was used in the treatment of a patient with severe hypoxaemia secondary to amniotic fluid embolism and for hypoxaemia secondary to the acute respiratory distress syndrome (ARDS) in a patient with acute on chronic liver failure and intra-abdominal sepsis. An apparent dose-response curve is demonstrated in the second case. A dose of IAP of 30–40 ng/kg/min produced an effect on oxygenation in the patient with liver failure equal to that seen at the maximal dose of (50 ng/kg/min). Reduction in dose below 30 ng/kg/min resulted in a deterioration in oxygenation towards baseline/pre-treatment levels. Inhaled aerosolized prostacyclin is a potent pulmonary vasodilator with little or no systemic hypotensive effect. It is simple to administer and would appear to be a viable alternative to inhaled nitric oxide.

Variable mortality rates have been reported for patients with rheumatic diseases admitted to an intensive care unit (ICU). Due to the absence of appropriate control groups in previous studies, it is not known whether the presence of a rheumatic disease constitutes a risk factor. Moreover, the accuracy of the Acute Physiology and Chronic Health Evaluation II (APACHE II) score for predicting outcome in this group of patients has been questioned. The primary goal of this study was to compare outcome of patients with rheumatic diseases admitted to a medical ICU to those of controls. The records of all patients admitted between 1 April 2003 and 30 June 2014 (n=4020) were screened for the presence of a rheumatic disease during admission (n=138). The diagnosis of a rheumatic disease was by standard criteria for these conditions. An age-and gender-matched control group of patients without a rheumatic disease was extracted from the patient population in the database during the same period (n=831). Mortality in ICU, in hospital and after 180 days did not differ significantly between patients with and without rheumatic diseases. There was no difference in the performance of the APACHE II score for predicting outcome in patients with rheumatic diseases and controls. This score, as well as a requirement for the use of inotropes or vasopressors, accurately predicted hospital mortality in the group of patients with rheumatic diseases. In conclusion, patients with a rheumatic condition admitted to intensive care do not do significantly worse than patients without such a disease.