ARC--augmented renal clearance.

In-hospital and intensive care unit mortality rates for sepsis remain un-acceptably high, and have prompted the publication of international guidelines on best practice. Crucial to this is the application of early appropriate antibacterial therapy, in the correct dose. However, antibacterial regimes in this setting have largely been extrapolated from those in healthy volunteers, and fail to consider the unique pathophysiology and treatment provided to this population. As such, augmented renal clearance (ARC) - the enhanced renal elimination of circulating solute - is likely to be one of the more common physiological changes encountered in this setting, although to date remains largely under-appreciated. Significantly this may alter the pharmacokinetics of many routinely prescribed agents in this setting, pre-disposing to subtherapeutic levels or treatment failure. This review paper examines this phenomenon in detail, providing a summary of the likely underlying mechanisms, those patients at greatest risk, and the implications for antibacterial dosing in the critically ill.

Augmented renal clearance in the Intensive Care Unit: an illustrative case series.

The substantial underlying disease burden, in combination with the therapeutic interventions provided, can result in significantly altered end-organ function in the critically ill. These changes can in turn affect key pharmacokinetic (PK) indices for many antibiotics, including drug clearance, promoting potentially subtherapeutic concentrations for lengthy periods of the dosing interval, therapeutic failure or the selection of resistant organisms. This paper presents three instructional cases from our tertiary-level Intensive Care Unit, where established antibiotic dosing regimens failed to achieve predefined PK targets for optimal bacterial killing. Using therapeutic drug monitoring (TDM), significant dose modification was subsequently undertaken. We propose augmented renal clearance as a possible mechanism underlying this phenomenon, particularly in young post-operative, burns or head-injured patients with normal serum creatinine concentrations. TDM, or at least a measured creatinine clearance, should be considered early in this setting to allow the optimisation of antibiotic exposure.

Muscle stretching technique increases vital capacity and range of motion in patients with chronic obstructive pulmonary disease.

OBJECTIVES: To determine if a specific hold and relax stretching technique was capable of (1) reversing the effect of tight chest wall muscles by increasing chest expansion, vital capacity, and shoulder range of motion and (2) decreasing perceived dyspnea and respiratory rate in persons with chronic obstructive pulmonary disease (COPD). DESIGN: Double-blind crossover trial. SETTING: A physiotherapy department at a major metropolitan hospital. PARTICIPANTS: Fourteen stable patients with COPD who had recently completed a pulmonary rehabilitation program were enrolled, with 10 patients completing the study. INTERVENTION: A hold and relax stretching technique of the pectoralis major and a sham technique each for 2 days. MAIN OUTCOME MEASURES: The primary outcome measure was vital capacity (VC), with secondary outcome measures being perceived dyspnea, axillary (ACE) and xiphisternal chest expansion (XCE), right and left shoulder horizontal extension, and respiratory rate. RESULTS: The hold and relax technique to the pectoralis major compared with the sham technique produced significant effects on VC (P<.01), and right (P<.01) and left (P<.05) upper-limb range of motion. There was no significant effect on ACE, XCE, perceived dyspnea, or respiratory rate. There was no order effect for either technique. CONCLUSIONS: The hold and relax technique produces short-term benefits in patients with COPD and should be investigated further.