Effect of albumin substitution on pharmacokinetics of piperacillin/tazobactam in patients with severe burn injury admitted to the ICU.

BACKGROUND: Pathophysiological changes in severely burned patients alter the pharmacokinetics (PK) of anti-infective agents, potentially leading to subtherapeutic concentrations at the target site. Albumin supplementation, to support fluid resuscitation, may affect pharmacokinetic properties by binding drugs. This study aimed to investigate the PK of piperacillin/tazobactam in burn patients admitted to the ICU before and after albumin substitution as total and unbound concentrations in plasma. PATIENTS AND METHODS: Patients admitted to the ICU and scheduled for 4.5 g piperacillin/tazobactam administration and 200 mL of 20% albumin substitution as part of clinical routine were included. Patients underwent IV microdialysis, and simultaneous arterial plasma sampling, at baseline and multiple timepoints after drug administration. PK analysis of total and unbound drug concentrations under steady-state conditions was performed before and after albumin supplementation. RESULTS: A total of seven patients with second- to third-degree burns involving 20%-60% of the total body surface were enrolled. Mean (SD) AUC0-8 (h·mg/L) of total piperacillin/tazobactam before and after albumin substitution were 402.1 (242)/53.2 (27) and 521.8 (363)/59.7 (32), respectively. Unbound mean AUC0-8 before and after albumin supplementation were 398.9 (204)/54.5 (25) and 456.4 (439)/64.5 (82), respectively. CONCLUSIONS: Albumin supplementation had little impact on the PK of piperacillin/tazobactam. After albumin supplementation, there was a numerical increase in mean AUC0-8 of total and unbound piperacillin/tazobactam, whereas similar Cmax values were observed. Future studies may investigate the effect of albumin supplementation on drugs with a higher plasma protein binding.

Occupational reintegration after severe burn injury: a questionnaire study.

BACKGROUND: As a consequence of improved survival rates after burn injury occupational reintegration of burn survivors has gained increasing significance. We aimed to develop a precise patient questionnaire as a tool to evaluate factors contributing to occupational reintegration. MATERIAL AND METHODS: A questionnaire comprising 20 questions specifically evaluating occupational reintegration was developed under psychological supervision. The single-center questionnaire study was implemented in patients with burn injuries who were admitted to the 6­bed burn intensive care unit (BICU) of the General Hospital of Vienna, Austria (2004-2013). The questionnaire was sent to burn survivors of working age (18-60 years) with an abbreviated burn severity index (ABSI) of 6 or greater, a total burn surface area (TBSA) of 15% or greater, and a BICU stay of at least 24 h. RESULTS: A total of 112 burn survivors met the inclusion criteria and were contacted by mail. Of the 112 patients 11 (10%) decided to participate in the study and 218/220 questions (99%) in 11 patients were answered. Out of 11 patients 7 (64%) reported successful return to work and 4 of 11 (36%) did not resume their occupation. Advanced age, longer BICU and hospital stays, higher TBSA, burn at work, lower education, and problems with esthetic appearance seemed to impair patients' return to their occupation. CONCLUSION: When implementing the questionnaire, severely burned patients with higher age, lower education, and longer hospital and BICU stay seemed at high risk for failed reintegration in their profession after burn injury.

Update on hyperbaric oxygen therapy in burn treatment.

Hyperbaric oxygen therapy (HBOT) has been shown to improve tissue hypoxia, neovascularization and ischemia reperfusion injury and reduce pathologic inflammation in various clinical settings and was proposed to be a game changer in treatment of burns. Improved and faster wound healing as well as a reduction of morbidity and mortality after thermal and concomitant carbon monoxide poisoning are expected. In defiance of the observed benefits for burn wounds and carbon monoxide poisoning in animal models and few randomized controlled trials there is an ongoing controversy regarding its use, indications and cost effectiveness. Furthermore, the use of HBOT, its indications and the evidence behind its efficiency are still widely unknown to most physicians involved in the treatment of burn patients. Therefore, a review of the up to date evidence-based literature was performed with a focus on available data of HBOT in burn care, to elaborate its use in acute thermal injury and carbon monoxide intoxication. Although beneficial effects of HBOT seem very likely insufficient evidence to support or disprove the routine use of HBOT in the treatment of burn care was found. Although difficult to carry out because of the high interindividual variability of burns and chronic wounds, the need for larger high-quality prospective randomized double-blinded controlled multicenter trials are necessary to be able to evaluate useful applications, expense and cost-efficiency of HBOT for burn care.

Incidence of risk factors for bloodstream infections in patients with major burns receiving intensive care: A retrospective single-center cohort study.

OBJECTIVES: The objective was primarily to identify risk factors for bloodstream infections (BSI) caused by different pathogens. METHODS: A retrospective single-center cohort study was performed on 472 burn patients with an abbreviated burn severity index (ABSI)≥3, a total burn surface area (TBSA)≥10%, and an ICU stay of at least 24h. Risk factors for different BSI pathogens were analyzed by competing risks regression model of Fine and Gray. RESULTS: A total of 114 burn patients developed 171 episodes of BSIs caused by gram-negative bacteria (n=78;46%), gram-positive bacteria (n=69;40%), and fungi (n=24;14%) median after 14days (range, 1-164), 16days (range, 1-170), and 16days (range, 0-89), respectively. A total of 24/114 patients (21%) had fatal outcomes. Isolation of the most common bloodstream isolates Enterococcus sp. (n=26), followed by Candida sp. and Pseudomonas sp. (n=22 for both) was significantly associated with increased TBSA (p≤0.006) and ABSI (p<0.0001) and need for fasciotomy (p<0.01). The death risk of patients with MDR gram-negative bacteremia was significantly increased by a hazard ratio of 12.6 (95% CI:4.8-32.8; p<0.0001). CONCLUSIONS: A greater TBSA and ABSI were associated with a significantly higher incidence of BSIs caused by Pseudomonas sp., Enterococcus sp. and Candida sp.

Non-occlusive mesenteric ischaemia: the prevalent cause of gastrointestinal infarction in patients with severe burn injuries.

BACKGROUND: Gastrointestinal complications occur frequently in intensive care patients with severe burns. Intestinal infarction and its deleterious consequences result in high mortality despite rapid surgical intervention. Our objective was to evaluate the aetiology of gastrointestinal infarction in intensive care patients with severe burns. STUDY DESIGN: We retrospectively evaluated all of the severe-burn victims at the burn unit of the Medical University of Vienna from 01/2002 to 06/2012 for whom a gastrointestinal infarction was diagnosed during their inpatient stay on computed-tomography, in the context of acute laparotomy, or upon autopsy by aetiology. RESULTS: After a severe thermal injury, 17 patients suffered a gastrointestinal infarction during their stay. In 82% of those patients, non-occlusive mesenteric ischaemia (NOMI) was identified as the cause of the gastrointestinal infarction. Patients with an embolic infarction tended to be older (78.0years embolism vs. 53.4 NOMI, mean, p<0.01), with a lower abbreviated burn severity index (8.7 embolism vs. 10.4 NOMI, mean, p<0.02) and a smaller total body surface area burned (20% embolism vs. 48% NOMI, mean, p<0.01) than those with a non-occlusive mesenterial ischaemia. No patients with an embolic infarction or any of the females in the entire gastrointestinal infarction group survived this event, resulting in a mortality rate of 100% for the embolic infarction group and female group. The decisive factor for surviving a NOMI was age (median age: male survivors 28years vs. nonsurvivors 66years (of this median, males=72years and females=60years), p<0.02). CONCLUSION: The results of our study clearly demonstrate that in severe-burn intensive care patients, non-occlusive mesenteric ischaemia is the most frequent cause of gastrointestinal infarction and that the decisive factor for survival is the patient's age.

Predisposing factors for candidemia in patients with major burns.

BACKGROUND: Despite advances in surgery and critical care, candidemia remains a significant cause of morbidity and mortality in patients with extensive burns. METHODS: A retrospective single-center cohort study was performed on 174 patients admitted to the Burn Intensive Care Unit of the General Hospital of Vienna (2007-2013). An AIC based model selection procedure for logistic regression models was utilized to identify factors associated with the presence of candidemia. RESULTS: Twenty (11%) patients developed candidemia on median day 16 after ICU admission associated with an increased overall mortality (30% versus 10%). Statistical analysis identified the following factors associated with proven candidemia: younger age (years) odds ratio (OR):0.96, 95% confidence interval (95% CI):0.92-1.0, female gender (reference male) OR:5.03, 95% CI:1.25-24.9, gastrointestinal (GI) complications requiring surgery (reference no GI complication) OR:20.37, 95% CI:4.25-125.8, non-gastrointestinal thromboembolic complications (reference no thromboembolic complication) OR:17.3, 95% CI:2.57-170.4 and inhalation trauma (reference no inhalation trauma) OR:7.96, 95% CI:1.4-48.4. CONCLUSIONS: Above-mentioned patient groups are at considerably high risk for candidemia and might benefit from a prophylactic antifungal therapy. Younger age as associated risk factor is likely to be the result of the fact that older patients with a great extent of burn body surface have a lower chance of survival compared to younger patients with a comparable TBSA.

Development of demographics and outcome of very old critically ill patients admitted to intensive care units.

PURPOSE: To evaluate the development of demographics and outcome of very old (>80 years) critically ill patients admitted to intensive care units. SETTING: All consecutive patients admitted to 41 Austrian intensive care units (ICUs) over an 11-year period. METHODS: We performed a retrospective cohort study of prospectively collected data. To compare parameters over time, patients were divided into three groups (group I from 1998 until 2001, group II from 2002 to 2004, and group III from 2005 to 2008). RESULTS: A total of 17,126 patients older than 80 years of age were admitted over the study period. The proportion of very old patients increased from 11.5% (I) to 15.3% (III) with a significant higher prevalence of females in all groups (on average 63.2%). Severity of illness also increased over time, even when corrected for age. Use of noninvasive mechanical ventilation increased over the years. However, risk-adjusted mortality rates [observed-to-expected (O/E) ratios] decreased from 1.14 [confidence interval (CI) 1.11-1.18] to 1.02 (CI 0.99-1.05). This improvement in outcome was confirmed on multivariate analysis: for every year delay in ICU admission, the odds to die decreased by 3%. Moreover, females exhibited a better outcome compared with males. CONCLUSIONS: The relative and absolute numbers of very old patients increased over the study period, as did the severity of illness. Despite this, risk-adjusted hospital mortality improved over the study period. Females dominated in the very old patients and exhibited moreover a better outcome compared with males.

The Veres adapter: clinical experience with a new device for jet ventilation via a laryngeal mask airway during flexible bronchoscopy.

BACKGROUND: A new device was developed to deliver high-frequency jet ventilation via a laryngeal mask airway (LMA). We investigated its use during flexible fiberoptic bronchoscopy in anesthetized patients. METHODS: Thirty adults were studied during interventional bronchoscopy. After facemask ventilation, the Veres adapter was connected to a size 4 or 5 LMA, and superimposed high-frequency jet ventilation was performed. Oxygen saturation, transcutaneous carbon dioxide, supraglottic airway pressure, and hemodynamic data were recorded and analyzed. RESULTS: Procedures were performed under stable hemodynamic conditions. Short procedure times and fast recovery were observed. Mild hypercapnia was the most common minor adverse effect (n = 16). One patient developed a pneumothorax after peripheral biopsy, 1 patient had a stiff chest during bronchoscopy, resulting in high airway pressures, and 1 patient required continuous positive airway pressure mask ventilation in the postoperative care unit. CONCLUSIONS: We report the clinical use of the Veres adapter in conjunction with an LMA to achieve rapid surgical access and adequate ventilation during flexible bronchoscopy. As an alternative to the use of an endotracheal tube, the new system may better maintain the airway during interventional and diagnostic bronchoscopy because of the larger diameter conduit.

Intrinsic positive end-expiratory pressure at various frequencies of supraglottic jet ventilation in a model of dynamic upper airway obstruction.

BACKGROUND: Supraglottic jet ventilation (JV(S)) with injectors above airway stenoses may result in inadvertent high lung pressures. We designed this study to investigate intrinsic positive end-expiratory pressure (PEEP(i)) during jet ventilation via a distant injector in a model of dynamic upper airway obstruction. METHODS: Respiratory pressure-time curves were recorded during JV(S) in a tracheal lung model using a pig's trachea and an embolectomy catheter's air-filled balloon to simulate 60 and 80% airway obstruction. JV(S) was performed at various jet frequencies (F(jet) 30 min(-1), 60 min(-1), and 100 min(-1)) and driving pressures (1 bar and 2 bar). RESULTS: JV(S) was associated with generation of PEEP(i), which depended on driving pressure, the degree of obstruction, and on ventilatory frequency. CONCLUSIONS: In the presence of a dynamic upper airway obstruction, JV(S) via a distant injector may result in PEEP(i), which cannot be detected when airway pressure is measured in front of the obstruction.

Airway stenosis-related increase of pulmonary pressure during high-frequency jet ventilation depends on injector's position.

BACKGROUND: High-frequency jet ventilation (HFJV) can lead to high-airway pressures under certain conditions. In this laboratory study, we evaluated the influence of the injector's position relative to a fixed airway obstruction on peak pressures in a tracheal-lung model. METHODS: We administered HFJV via a metal jet injector at varying distances from connectors simulating laryngotracheal airway stenosis. Peak pressures were measured inside the lung model. RESULTS: When the jet nozzle was near the simulated stenosis, peak pressure within the test lung increased and reached a maximum when the stenosis' lumen decreased despite unchanged parameters of jet gas flow. With the injector's tip placed 8-10 cm in front of the stenosis, reduction of airway diameter did not result in an increase of distal peak pressures. These observations were similar for all settings of gas flow (0.5-1.5 bar driving pressure) and frequencies. CONCLUSION: This study in a lung model suggests that placing an injector more than 8 cm proximal to a laryngotracheal stenosis will prevent changes in intrapulmonary pressure related to the degree of stenosis or driving pressure during HFJV. The location of the injector chosen for clinical care should balance the need for effective ventilation with the risk of barotrauma.

Spinal versus general anesthesia for orthopedic surgery: anesthesia drug and supply costs.

Total hip or knee replacement surgeries are common orthopedic interventions that can be performed with spinal anesthesia (SA) or general anesthesia (GA). No study has investigated the economic aspects associated with the two anesthetic techniques for this common surgery. We randomized 40 patients to receive either SA or GA and analyzed the drug and supply costs for anesthesia und recovery. Anesthesia-related times, hemodynamic variables, and pain scores were also recorded. Total costs per case without personnel costs were almost half in the SA group compared with the GA group; this was a result of less cost for anesthesia (P < 0.01) and for recovery (P < 0.05). This finding was supported by a sensitivity analysis. There were no relevant differences regarding anesthesia-related times. Patients in the GA group were admitted to the postanesthesia care unit with a higher pain score and needed more analgesics than patients in the SA group (both P < 0.01). We conclude that SA is a more cost-effective alternative to GA in patients undergoing hip or knee replacement, as it is associated with lower fixed and variable costs. Moreover, SA seems to be more effective, as patients in the SA group showed lower postoperative pain scores during their stay in the postanesthesia care unit.

[Perioperative pain management at the department of orthopaedic surgery of the Vienna Medical School]. / Perioperatives Schmerzmanagement an der Universitätsklinik für Orthopädie Wien.

Surgical treatment in the skeleton region and its adjacent tissue causes severe pain, demonstrated by the high demand of anaesthetics in the early postoperative phase. In order to offer adequate and individually adapted pain management, the orthopaedic department is working closely with the departments of anaesthesiology and intensive care medicine of the Vienna Medical University at the Vienna's General Hospital. The aim of this cooperation is to start postoperative rehabilitation early, to increase postoperative quality of life and to reduce the length of hospital stay. The surgical spectrum of the orthopaedic department consists of general orthopaedic, paediatric-orthopaedic-, sport- and rheuma-orthopaedic, tumour and spine interventions. The purpose of this review is to describe the cooperation between orthopaedic surgeons and anaesthetists at the Vienna Medical University.

Alveolar recruitment of atelectasis under combined high-frequency jet ventilation: a computed tomography study.

OBJECTIVE: To quantify the effect of superimposed high-frequency jet ventilation on lung recruitment in adult patients with acute lung injury. DESIGN AND SETTING: Prospective clinical study in the intensive care unit of a university teaching hospital. PATIENTS: Eight adults suffering from acute lung injury with a mean lung injury score of 2.6+/-0.6 and pronounced atelectasis in at least two lung quadrants. The cause was either pneumonia ( n=5) or postoperative sepsis ( n=3). INTERVENTIONS: Superimposed high-frequency jet ventilation was initiated in patients following a mean of 4.4+/-1.7 days of conventional ventilation. Before and 4 h after the start of superimposed high-frequency jet ventilation differential lung volumes were determined by volumetry using computed tomography. MEASUREMENTS AND RESULTS: Superimposed high-frequency jet ventilation significantly increased the lung volume of every patient due to alveolar recruitment. This was achieved despite lower peak inspiratory pressures and higher PaO(2)/FIO(2) ratios than with conventional ventilation. CONCLUSIONS: Treatment with superimposed high-frequency jet ventilation for 4 h resulted in rapid alveolar recruitment in dependent lung areas, improved gas exchange, and better arterial oxygenation. It offers an effective and advantageous alternative to conventional ventilation for ventilatory management of respiratory insufficient patients.