Sedatives, analgesics, and antipsychotics in tracheostomised intensive care unit patients – Is less more?

Background: Sedation and anaesthesia are used universally to facilitate mechanical ventilation – with larger cumulative doses being used in those with prolonged ventilation. Transitioning from an endotracheal to a tracheostomy tube enables the depth of sedation to be reduced. Early use of speaking valves with tracheostomised patients has become routine in some intensive care units (ICUs). The return of verbal communication has been observed to improve ease of patient care and increase patient and family engagement, with a perceived reduction in patient agitation. Objectives: The objective of this study was to investigate the potential impact of speaking valve (SV) use on requirements of sedatives, analgesics, and antipsychotics in ICU patients with a tracheostomy tube. Methods: A retrospective data audit was undertaken for all tracheostomised patients in a cardiorespiratory ICU from 2011 to 2014. Use of sedative, analgesic, and antipsychotic drugs was captured for endotracheal tube, tracheostomy tube, and SV periods, including patient demographics, disease specifics, and severity. Results: A total of 145 patients received an SV, and 115 did not. There were significantly less (p < 0.001) analgesic drugs used after introduction of SVs into the ICU (2011 vs 2012–2014). In the final adjusted multivariable model, analgesic dose was associated with age, positive extracorporeal membrane oxygenation (ECMO) status, and attendance to operating theatre during ICU admission. The only variable associated with sedative dose was age. Receiving any antipsychotics was associated with gender (less likely in females: odds ratio, 0.4; 95% confidence interval, 0.3–0.7), length of stay [more likely with stay over 25 days (odds ratio, 3.1; 95% confidence interval, 1.4–0.8) compared with 5–11 days], and survival. Conclusions: There was significantly fewer analgesics used after the introduction of SVs. However, SV use in patients with tracheostomy tube was not found to be associated with reduced dose of sedatives or antipsychotics, despite the clinical impression. Future prospective studies are needed to more adequately investigate the association between drugs and patients' ability to verbally participate in their care

Use of acid suppression medications in postoperative cardiac surgical intensive care unit patients

Background: Acid suppression medications are routinely used in general intensive care unit patients for prevention of stress-related gastric mucosal bleeding. Their use has been extrapolated to include elective postoperative cardiac surgical patients. The evidence for their use in this group of patients remains inconclusive (Shin and Abah, Interact Cardiovasc Thorac Surg, 2012; 14: 622-8). Aim: To audit the use of acid suppression therapy in postoperative cardiac surgical patients as inpatients and after discharge, and ascertain whether these patients experienced postoperative gastrointestinal bleeding. Method: A retrospectivechart review was undertaken, focusing on cases of cardiac surgical intensive care patients to investigate the use of stress ulcer prophylaxis and the occurrence of post-surgical gastrointestinal bleeding. Tine continuation of therapy after discharge was also audited. Results: The cases of 78 patients were included in the audit: all received stress ulcer prophylaxis, and no patients experienced gastrointestinal bleeding postoperatively. In all, 27% of these patients weredispensed acid suppression therapy without a valid indication at the time of discharge. Conclusions: It cannot be conclusively determined if the absence of postoperative gastrointestinal bleeding was due to the administration Of prophylaxis. An alternative explanation is that stress ulcers were not likely to occur in this cohort of patients. Despite not having any indication for continuation of acid suppression, 20 patients were discharged with these medications

Increased sedation requirements in patients receiving extracorporeal membrane oxygenation for respiratory and cardio-respiratory failure

Critically ill patients receiving extracorporeal membrane oxygenation (ECMO) are often noted to have increased sedation requirements. However, data related to sedation in this complex group of patients is limited. The aim of our study was to characterise the sedation requirements in adult patients receiving ECMO for cardiorespiratory failure. A retrospective chart review was performed to collect sedation data for 30 consecutive patients who received venovenous or venoarterial ECMO between April 2009 and March 2011. To test for a difference in doses over time we used a regression model. The dose of midazolam received on ECMO support increased by an average of 18 mg per day (95% confidence interval 8, 29 mg, P=0.001), while the dose of morphine increased by 29 mg per day (95% confidence interval 4, 53 mg, P=0.021) The venovenous group received a daily midazolam dose that was 157 mg higher than the venoarterial group (95% confidence interval 53, 261 mg, P=0.005). We did not observe any significant increase in fentanyl doses over time (95% confidence interval 1269, 4337 µg, P=0.94). There is a significant increase in dose requirement for morphine and midazolam during ECMO. Patients on venovenous ECMO received higher sedative doses as compared to patients on venoarterial ECMO. Future research should focus on mechanisms behind these changes and also identify drugs that are most suitable for sedation during ECMO

Dexmedetomidine prescribing in Australian intensive care units: an observational study

Dexmedetomidine is used in the intensive care unit (ICU) as a short-term sedative. The data included in the manufacturer's product information is controversial, and there is little consensus to guide initial dosing and titration. This observational study surveyed the practice of dexmedetomidine use in Australian ICUs. An expression of interest (EOI) for a multisite observational study was sent to members of the ICU email group of the Society of Hospital Pharmacists Australia (SHPA). Participating members collected treatment-related data for patients meeting inclusion criteria between January 2013 and July 2014. Six of 14 sites that responded positively to the EOI returned complete datasets, and 232 patients met the inclusion criteria. The main reported indications for dexmedetomidine use across the six sites were to manage agitation (33.2%), to aid extubation (32.8%) and to sedate (34.0%). The median duration of therapy was 42\ua0h (range 1–672\ua0h). Only nine patients (3.9%) received loading doses. The median maximum dose used for maintenance therapy in patients ranged from 1.2 to 4.0 microgram/kg per h. There was a significant disparity of practice across sites, as evidenced by differences in reported indication, off-label use, rates of loading doses and doses used for maintenance therapy. Consensus prescribing guidelines are required to guide more consistent and evidence-based prescribing of dexmedetomidine

Sequestration of drugs in the circuit may lead to therapeutic failure during extracorporeal membrane oxygenation

Introduction Extracorporeal membrane oxygenation (ECMO) is a supportive therapy, with its success dependent on effective drug therapy that reverses the pathology and/or normalizes physiology. However, the circuit that sustains life can also sequester life-saving drugs, thereby compromising the role of ECMO as a temporary support device. This ex vivo study was designed to determine the degree of sequestration of commonly used antibiotics, sedatives and analgesics in ECMO circuits. Methods Four identical ECMO circuits were set up as per the standard protocol for adult patients on ECMO. The circuits were primed with crystalloid and albumin, followed by fresh human whole blood, and were maintained at a physiological pH and temperature for 24 hours. After baseline sampling, fentanyl, morphine, midazolam, meropenem and vancomycin were injected into the circuit at therapeutic concentrations. Equivalent doses of these drugs were also injected into four polyvinylchloride jars containing fresh human whole blood for drug stability testing. Serial blood samples were collected from the ECMO circuits and the controls over 24 hours and the concentrations of the study drugs were quantified using validated assays. Results Four hundred samples were analyzed. All study drugs, except meropenem, were chemically stable. The average drug recoveries from the ECMO circuits and the controls at 24 hours relative to baseline, respectively, were fentanyl 3% and 82%, morphine 103% and 97%, midazolam 13% and 100%, meropenem 20% and 42%, vancomycin 90% and 99%. There was a significant loss of fentanyl (p = 0.0005), midazolam (p = 0.01) and meropenem (p = 0.006) in the ECMO circuit at 24 hours. There was no significant circuit loss of vancomycin at 24 hours (p = 0.26). Conclusions Sequestration of drugs in the circuit has implications on both the choice and dosing of some drugs prescribed during ECMO. Sequestration of lipophilic drugs such as fentanyl and midazolam appears significant and may in part explain the increased dosing requirements of these drugs during ECMO. Meropenem sequestration is also problematic and these data support a more frequent administration during ECMO

Incremental research approach to describing the pharmacokinetics of ciprofloxacin during extracorporeal membrane oxygenation

Significant interactions between drugs, extracorporeal membrane oxygenation (ECMO) circuits and critical illness may affect the pharmacokinetic properties of antibiotics in critically ill patients receiving ECMO.To describe the pharmacokinetic properties of ciprofloxacin during ECMO by integrating pre-clinical findings (ie, ex vivo and in vivo ovine models) to a critically ill patient.An ex vivo model of an ECMO circuit was used to describe ciprofloxacin concentration changes over 24 hours. An in vivo ovine model of ECMO was used to describe the population pharmacokinetic properties of ciprofloxacin in three different groups of sheep, and to investigate sources of pharmacokinetic variability. In the final phase, data from a 39-year-old critically ill man was used to validate the findings from the ovine pharmacokinetic model.In the ex vivo model of ECMO circuits, the median concentrations of ciprofloxacin at baseline and at 24 hours after ciprofloxacin infusion were similar. The time course of ciprofloxacin in the in vivo ovine on ECMO model was adequately described by a two-compartment model. The final population primary parameter mean estimates were: clearance (CL), 0.21 L/kg/h (SD, 0.09 L/kg/h) and volume of distribution (Vd), 0.84 L/kg (SD, 0.12 L/kg). In the critically ill ECMO patient, the primary pharmacokinetic parameter estimates were: CL, 0.15 L/kg/h and Vd, 0.99 L/kg.We provide preliminary evidence that ciprofloxacin dosing in ECMO patients should remain in line with the recommended dosing strategies for critically ill patients not receiving ECMO