Pressure-adjusted venting eliminates start-up delays and compensates for vertical position of syringe infusion pumps used for microinfusion.

Microinfusions are commonly used for the administration of catecholamines, but start-up delays pose a problem for reliable and timely drug delivery. Recent findings show that venting of the syringe infusion pump with draining of fluid to ambient pressure before directing the flow towards the central venous catheter does not counteract start-up delays. With the aim to reduce start-up delays, this study compared fluid delivery during start-up of syringe infusion pumps without venting, with ambient pressure venting, and with central venous pressure (CVP)-adjusted venting. Start-up fluid delivery from syringe pumps using a microinfusion of 1 mL/h was assessed by means of liquid flow measurement at 10, 60, 180 and 360 s after opening the stopcock and starting the pump. Assessments were performed using no venting, ambient pressure venting or CVP-adjusted venting, with the pump placed either at zero, - 43 cm or + 43 cm level and exposed to a simulated CVP of 10 mmHg. Measured fluid delivery was closest to the calculated fluid delivery for CVP-adjusted venting (87% to 100% at the different timepoints). The largest deviations were found for ambient pressure venting (- 1151% to + 82%). At 360 s after start-up 72% to 92% of expected fluid volumes were delivered without venting, 46% to 82% with ambient pressure venting and 96% to 99% with CVP-adjusted venting. CVP-adjusted venting demonstrated consistent results across vertical pump placements (p = 0.485), whereas the other methods had significant variances (p < 0.001 for both). In conclusion, CVP-adjusted venting effectively eliminates imprecise drug delivery and start-up delays when using microinfusions.

Evaluation of the venting principle to reduce start-up delays in syringe infusion pumps used for microinfusions.

Start-up delays of syringe pump assemblies can impede the timely commencement of an effective drug therapy when using microinfusions in hemodynamically unstable patients. The application of the venting principle has been proposed to eliminate start-up delays in syringe pump assemblies. However, effectively delivered infusion volumes using this strategy have so far not been measured. This invitro study used two experimental setups to measure the effect of the venting principle compared to a standard non-venting approach on delivered start-up infusion volumes at various timepoints, backflow volumes, flow inversion and zero drug delivery times by means of liquid flow measurements at flow rates of 0.5, 1.0 and 2.0 mL/h. Measured delivered initial start-up volumes were negative with all flow rates in the vented and non-vented setup. Maximum backflow volumes were 1.8 [95% CI 1.6 to 2.3] times larger in the vented setup compared to the non-vented setup (p < 0.0001). Conversely, times until flow inversion were 1.5 [95% CI 1.1 to 2.9] times shorter in the vented setup (p < 0.002). This led to comparable zero drug delivery times between the two setups (p = 0.294). Start-up times as defined by the achievement of at least 90% of steady state flow rate were achieved faster with the vented setup (p < 0.0001), but this was counteracted by the increased backflow volumes. The application of the venting principle to the start-up of microinfusions does not improve the timely delivery of drugs to the patient since the faster start-up times are counteracted by higher backflow volumes when opening the three-way stopcock.

Effect of vertical pump position on start-up fluid delivery of syringe pumps used for microinfusion.

BACKGROUND: Connection and opening a syringe infusion pump to a central venous line can lead to acute anterograde or retrograde fluid shifts depending on the level of central venous pressure. This may lead to bolus events or to prolonged lag times of intravenous drug delivery, being particularly relevant when administering vasoactive or inotropic drugs in critically ill patients using microinfusion. The aim of this study was to assess the effect of syringe pump positioning at different vertical heights on start-up fluid delivery before versus after purging and connection the pump to the central venous catheter. METHODS: This in vitro study measured ante- and retrograde infusion volumes delivered to the central venous line after starting the syringe pump at a set infusion rate of 1 mL/h. In setup one, the pump was first positioned to vertical levels of +43 cm or -43 cm and then purged and connected to a central venous catheter. In setup two, the pump was first purged and connected at zero level and secondarily positioned to a vertical level of +43 cm or -43 cm. Central venous pressure was adjusted to 10 mmHg in both setups. RESULTS: Positioning of the pump prior to purging and connection to the central venous catheter resulted in a better start-up performance with delivered fluid closer to programmed and expected infusion volumes when compared to the pump first purged, connected, and then positioned. Significant backflow volumes were observed with the pump purged and connected first and then positioned below zero level. No backflow was measured with the pump positioned first below zero level and then purged and connected. CONCLUSIONS: Syringe infusion pump assemblies should be positioned prior to purging and connection to a central venous catheter line when starting a new drug, particularly when administering highly concentrated vasoactive or inotropic drugs delivered at low flow rates.

Human-AI teaming: leveraging transactive memory and speaking up for enhanced team effectiveness.

In this prospective observational study, we investigate the role of transactive memory and speaking up in human-AI teams comprising 180 intensive care (ICU) physicians and nurses working with AI in a simulated clinical environment. Our findings indicate that interactions with AI agents differ significantly from human interactions, as accessing information from AI agents is positively linked to a team's ability to generate novel hypotheses and demonstrate speaking-up behavior, but only in higher-performing teams. Conversely, accessing information from human team members is negatively associated with these aspects, regardless of team performance. This study is a valuable contribution to the expanding field of research on human-AI teams and team science in general, as it emphasizes the necessity of incorporating AI agents as knowledge sources in a team's transactive memory system, as well as highlighting their role as catalysts for speaking up. Practical implications include suggestions for the design of future AI systems and human-AI team training in healthcare and beyond.

Coagulation side effects of enzymatic debridement in burned patients.

OBJECTIVES: Bromelain-based enzymatic debridement has emerged as a valuable option to the standard surgical intervention for debridement in burn injuries. Adverse effects on coagulation parameters after enzymatic debridement have been described. The purpose of this study was to compare the effect of enzymatic and surgical debridement on coagulation. METHODS: Between 03/2017 and 02/2021 patients with burn injuries with a total body surface area (TBSA) ≥ 1% were included in the study. Patients were categorized into two groups: the surgically debrided group and the enzymatically debrided group. Coagulation parameters were assessed daily for the first seven days of hospitalization. RESULTS: In total 132 patients with a mean TBSA of 17% were included in this study, of which 66 received enzymatic debridement and 66 received regular surgical-debridement. Patients receiving enzymatic debridement presented significantly higher factor-V concentration values over the first seven days after admission (p = <0.01). Regarding coagulation parameters, we found no difference in INR-, aPTT-, fibrinogen-, factor-XIII- and thrombocyte-concentrations over the first seven days (p = >0.05). CONCLUSION: Enzymatic debridement in burned patients does not appear to increase the risk of coagulation abnormalities compared with the regular surgical approach.

Perioperative targeted temperature management of severely burned patients by means of an oesophageal temperature probe.

BACKGROUND: Hypothermia in severely burned patients is associated with a significant increase in morbidity and mortality. The use of an oesophageal heat exchanger tube (EHT) can improve perioperative body temperatures in severely burned patients. The aim of this study was to investigate the intraoperative warming effect of oesophageal heat transfer in severe burn patients. METHODS: Single-centre retrospective study performed at the Burns Centre of the University Hospital Zurich. Between January 2020 and May 2021 perioperative temperature management with EHT was explored in burned patients with a total body surface area (TBSA) larger than 30%. Data from patients, who received perioperative temperature management by EHT, were compared to data from the same patients during interventions performed under standard temperature management matching for length and type of intervention. RESULTS: A total of 30 interventions (15 with and 15 without EHT) in 10 patients were analysed. Patient were 38 [26-48] years of age, presented with severe burns covering a median of 50 [42-64] % TBSA and were characterized by an ABSI of 10 [8-12] points. When receiving EHT management patients experienced warming at 0.07 °C per minute (4.2 °C/h) compared to a temperature loss of - 0.03 °C per minute (1.8 °C/h) when only receiving standard temperature management (p < 0.0001). No adverse or serious adverse events were reported. CONCLUSION: The use of an oesophageal heat transfer device was effective and safe in providing perioperative warming to severely burned patients when compared to a standard temperature management protocol. By employing an EHT as primary temperature management device perioperative hypothermia in severely burned patients can possibly be averted, potentially leading to reduced hypothermia-associated complications.

Long-term ketamine infusion-induced cholestatic liver injury in COVID-19-associated acute respiratory distress syndrome.

BACKGROUND: A higher-than-usual resistance to standard sedation regimens in COVID-19 patients suffering from acute respiratory distress syndrome (ARDS) has led to the frequent use of the second-line anaesthetic agent ketamine. Simultaneously, an increased incidence of cholangiopathies in mechanically ventilated patients receiving prolonged infusion of high-dose ketamine has been noted. Therefore, the objective of this study was to investigate a potential dose-response relationship between ketamine and bilirubin levels. METHODS: Post hoc analysis of a prospective observational cohort of patients suffering from COVID-19-associated ARDS between March 2020 and August 2021. A time-varying, multivariable adjusted, cumulative weighted exposure mixed-effects model was employed to analyse the exposure-effect relationship between ketamine infusion and total bilirubin levels. RESULTS: Two-hundred forty-three critically ill patients were included into the analysis. Ketamine was infused to 170 (70%) patients at a rate of 1.4 [0.9-2.0] mg/kg/h for 9 [4-18] days. The mixed-effects model revealed a positively correlated infusion duration-effect as well as dose-effect relationship between ketamine infusion and rising bilirubin levels (p < 0.0001). In comparison, long-term infusion of propofol and sufentanil, even at high doses, was not associated with increasing bilirubin levels (p = 0.421, p = 0.258). Patients having received ketamine infusion had a multivariable adjusted competing risk hazard of developing a cholestatic liver injury during their ICU stay of 3.2 [95% confidence interval, 1.3-7.8] (p = 0.01). CONCLUSIONS: A causally plausible, dose-effect relationship between long-term infusion of ketamine and rising total bilirubin levels, as well as an augmented, ketamine-associated, hazard of cholestatic liver injury in critically ill COVID-19 patients could be shown. High-dose ketamine should be refrained from whenever possible for the long-term analgosedation of mechanically ventilated COVID-19 patients.

Hyperinflammatory environment drives dysfunctional myeloid cell effector response to bacterial challenge in COVID-19.

COVID-19 displays diverse disease severities and symptoms including acute systemic inflammation and hypercytokinemia, with subsequent dysregulation of immune cells. Bacterial superinfections in COVID-19 can further complicate the disease course and are associated with increased mortality. However, there is limited understanding of how SARS-CoV-2 pathogenesis and hypercytokinemia impede the innate immune function against bacterial superinfections. We assessed the influence of COVID-19 plasma hypercytokinemia on the functional responses of myeloid immune cells upon bacterial challenges from acute-phase COVID-19 patients and their corresponding recovery-phase. We show that a severe hypercytokinemia status in COVID-19 patients correlates with the development of bacterial superinfections. Neutrophils and monocytes derived from COVID-19 patients in their acute-phase showed an impaired intracellular microbicidal capacity upon bacterial challenges. The impaired microbicidal capacity was reflected by abrogated MPO and reduced NETs production in neutrophils along with reduced ROS production in both neutrophils and monocytes. Moreover, we observed a distinct pattern of cell surface receptor expression on both neutrophils and monocytes, in line with suppressed autocrine and paracrine cytokine signaling. This phenotype was characterized by a high expression of CD66b, CXCR4 and low expression of CXCR1, CXCR2 and CD15 in neutrophils and low expression of HLA-DR, CD86 and high expression of CD163 and CD11b in monocytes. Furthermore, the impaired antibacterial effector function was mediated by synergistic effect of the cytokines TNF-α, IFN-γ and IL-4. COVID-19 patients receiving dexamethasone showed a significant reduction of overall inflammatory markers in the plasma as well as exhibited an enhanced immune response towards bacterial challenge ex vivo. Finally, broad anti-inflammatory treatment was associated with a reduction in CRP, IL-6 levels as well as length of ICU stay and ventilation-days in critically ill COVID-19 patients. Our data provides insights into the transient functional dysregulation of myeloid immune cells against subsequent bacterial infections in COVID-19 patients and describe a beneficial role for the use of dexamethasone in these patients.

Key Factors in Decision Making for ECLS: A Binational Factorial Survey.

BACKGROUND: Extracorporeal life support (ECLS) provides support to patients with cardiopulmonary failure refractory to conventional therapy. While ECLS is potentially life-saving, it is associated with severe complications; decision making to initiate ECLS must, therefore, carefully consider which patients ECLS potentially benefits despite its consequences. OBJECTIVE: To answer 2 questions: First, which medically relevant patient factors influence decisions to initiate ECLS? Second, what are factors relevant to decisions to withdraw a running ECLS treatment? METHODS: We conducted a factorial survey among 420 physicians from 111 hospitals in Switzerland and Germany. The study included 2 scenarios: 1 explored willingness to initiate ECLS, and 1 explored willingness to withdraw a running ECLS treatment. Each participant responded to 5 different vignettes for each scenario. Vignettes were analyzed using mixed-effects regression models with random intercepts. RESULTS: Factors in the vignettes such as patients' age, treatment costs, therapeutic goal, comorbidities, and neurological outcome significantly influenced the decision to initiate ECLS. When it came to the decision to withdraw ECLS, patients' age, days on ECLS, criteria for discontinuation, condition of the patient, comorbidities, and neurological outcome were significant factors. In both scenarios, patients' age and neurological outcome were the most influential factors. CONCLUSIONS: This study provided insights into physicians' decision making processes about ECLS initiation and withdrawal. Patients' age and neurological status were the strongest factors influencing decisions regarding initiation of ECLS as well as for ECLS withdrawal. The findings may contribute to a more refined understanding of complex decision making for ECLS.

Antimicrobial susceptibility patterns of respiratory Gram-negative bacterial isolates from COVID-19 patients in Switzerland.

BACKGROUND: Bacterial superinfections associated with COVID-19 are common in ventilated ICU patients and impact morbidity and lethality. However, the contribution of antimicrobial resistance to the manifestation of bacterial infections in these patients has yet to be elucidated. METHODS: We collected 70 Gram-negative bacterial strains, isolated from the lower respiratory tract of ventilated COVID-19 patients in Zurich, Switzerland between March and May 2020. Species identification was performed using MALDI-TOF; antibiotic susceptibility profiles were determined by EUCAST disk diffusion and CLSI broth microdilution assays. Selected Pseudomonas aeruginosa isolates were analyzed by whole-genome sequencing. RESULTS: Pseudomonas aeruginosa (46%) and Enterobacterales (36%) comprised the two largest etiologic groups. Drug resistance in P. aeruginosa isolates was high for piperacillin/tazobactam (65.6%), cefepime (56.3%), ceftazidime (46.9%) and meropenem (50.0%). Enterobacterales isolates showed slightly lower levels of resistance to piperacillin/tazobactam (32%), ceftriaxone (32%), and ceftazidime (36%). All P. aeruginosa isolates and 96% of Enterobacterales isolates were susceptible to aminoglycosides, with apramycin found to provide best-in-class coverage. Genotypic analysis of consecutive P. aeruginosa isolates in one patient revealed a frameshift mutation in the transcriptional regulator nalC that coincided with a phenotypic shift in susceptibility to ß-lactams and quinolones. CONCLUSIONS: Considerable levels of antimicrobial resistance may have contributed to the manifestation of bacterial superinfections in ventilated COVID-19 patients, and may in some cases mandate consecutive adaptation of antibiotic therapy. High susceptibility to amikacin and apramycin suggests that aminoglycosides may remain an effective second-line treatment of ventilator-associated bacterial pneumonia, provided efficacious drug exposure in lungs can be achieved.

Efficient treatment of esophageal nutrition bezoars: dissolution outmatches removal-the Zurich approach.

Enteral feed bezoars are difficult to treat and can lead to serious adverse events. There is no standardized treatment approach and various strategies have been suggested. We herein describe three cases of successful dissolutions of feed bezoars consisting of Promote® Fibre Plus with sodium bicarbonate 8.4% in critically ill patients. To provide the rationale for this approach, the effect of sodium bicarbonate 8.4% on enteral feed concretions was studied in vitro. First, Promote® Fibres Plus was incubated with hydrochloric acid with gradually decreasing pH values to establish a pH at which the solution solidifies. The resulting enteral feed concretion was exposed to sodium bicarbonate 8.4% and Coca Cola®. All patients were successfully treated with sodium bicarbonate 8.4% without the need of lengthy or repeat endoscopies. In vitro, Promote® Fibres Plus solidifies when acidified below a pH of 4.6. The resulting enteral feed concretions dissolved when exposed to sodium bicarbonate 8.4%. Incubation with Coca Cola® had no effect. We provide evidence that enteral feed bezoars consisting of Promote® Fibres Plus can be efficiently and safely treated with sodium bicarbonate 8.4% offering a new approach for daily patient care.

Incidence and Time Point of Sepsis Detection as Related to Different Sepsis Definitions in Severely Burned Patients and Their Accompanying Time Course of Pro-Inflammatory Biomarkers.

BACKGROUND: Diagnosis of sepsis in burn patients remains difficult for various reasons. One major problem is the definition of sepsis itself. Therefore, previous and current sepsis definitions are a matter of ongoing validation, but a well-defined consensus on which clinical and laboratory parameters to incorporate in such a definition is lacking. The aim of the present study was to compare the incidence and time-related occurrence of septic events according to different definitions as well as their accompanying time course of pro-inflammatory biomarkers. METHODS: Across the first 14 days after admission, the incidence and time point of sepsis according to three different definitions (Sepsis-3, Sepsis American Burns Association [ABA] 2007, Sepsis Zurich Burn Center) were assessed on a daily basis in adult burn patients with total body surface area (TBSA) ≥15% admitted to the Zurich Burn Center between May 2015 and October 2018. In order to investigate how well daily drawn proinflammatory biomarkers (white blood cells (WBCs), C-reactive protein (CRP), procalcitonin (PCT), and novel pancreatic stone protein (PSP)) reflect the progression of sepsis depending on its type of definition, a longitudinal mixed model analysis was performed across the first 14 days for septic and non-septic patients. Additionally, the relative increase of biomarker levels 24, 48, and 72 h prior to a septic event was analyzed for each definition used. RESULTS: In our cohort of 90 severely burned patients, Sepsis-3 identified 46 patients (51.1%) as septic, while ABA 2007 and the Zurich Burn Center definition counted 33 patients (36.7%) and 24 patients (26.6%), respectively. Sepsis-3 detected sepsis about 1 day earlier than Sepsis ABA 2007 (p < 0.001) and about 0.5 days earlier than Sepsis Zurich Burn Center (p = 0.04). The course of pro-inflammatory biomarkers was largely unaffected by the type of sepsis definition. Irrespective of the sepsis definition, PSP was the only marker to demonstrate a highly significant interaction between time and group (sepsis versus no sepsis) (p < 0.001) with a 3.3-5.5-fold increase within 72 h before the event of sepsis, whereas CRP, PCT, and WBC showed only mild undulations. CONCLUSIONS: Despite the ongoing dilemma of how to define sepsis in burn patients, a continually calculated SOFA score as used in Sepsis-3 is advantageous to early identify a patient's detrimental progression to sepsis. Inclusion of biomarkers, such as PSP, may help support the burn specialist's diagnosis of sepsis and could improve the diagnostic performance of current and future definitions in burn patients.

Closed-Loop Versus Conventional Mechanical Ventilation in COVID-19 ARDS.

BACKGROUND: Lung-protective ventilation is key in bridging patients suffering from COVID-19 acute respiratory distress syndrome (ARDS) to recovery. However, resource and personnel limitations during pandemics complicate the implementation of lung-protective protocols. Automated ventilation modes may prove decisive in these settings enabling higher degrees of lung-protective ventilation than conventional modes. METHOD: Prospective study at a Swiss university hospital. Critically ill, mechanically ventilated COVID-19 ARDS patients were allocated, by study-blinded coordinating staff, to either closed-loop or conventional mechanical ventilation, based on mechanical ventilator availability. Primary outcome was the overall achieved percentage of lung-protective ventilation in closed-loop versus conventional mechanical ventilation, assessed minute-by-minute, during the initial 7 days and overall mechanical ventilation time. Lung-protective ventilation was defined as the combined target of tidal volume <8 ml per kg of ideal body weight, dynamic driving pressure <15 cmH2O, peak pressure <30 cmH2O, peripheral oxygen saturation ≥88% and dynamic mechanical power <17 J/min. RESULTS: Forty COVID-19 ARDS patients, accounting for 1,048,630 minutes (728 days) of cumulative mechanical ventilation, allocated to either closed-loop (n = 23) or conventional ventilation (n = 17), presenting with a median paO2/ FiO2 ratio of 92 [72-147] mmHg and a static compliance of 18 [11-25] ml/cmH2O, were mechanically ventilated for 11 [4-25] days and had a 28-day mortality rate of 20%. During the initial 7 days of mechanical ventilation, patients in the closed-loop group were ventilated lung-protectively for 65% of the time versus 38% in the conventional group (Odds Ratio, 1.79; 95% CI, 1.76-1.82; P < 0.001) and for 45% versus 33% of overall mechanical ventilation time (Odds Ratio, 1.22; 95% CI, 1.21-1.23; P < 0.001). CONCLUSION: Among critically ill, mechanically ventilated COVID-19 ARDS patients during an early highpoint of the pandemic, mechanical ventilation using a closed-loop mode was associated with a higher degree of lung-protective ventilation than was conventional mechanical ventilation.

Pancreatic Stone Protein Predicts Sepsis in Severely Burned Patients Irrespective of Trauma Severity: A Monocentric Observational Study.

OBJECTIVE: The burn victim's inherent state of hyperinflammation frequently camouflages septic events delaying the initiation of targeted intensive care therapy. Accurate biomarkers are urgently needed to support sepsis detection before patients' clinical deterioration. SUMMARY OF BACKGROUND DATA: Evidence on the usefulness of pancreatic stone protein (PSP) as a powerful diagnostic and prognostic marker in critically ill patients has recently accumulated. METHODS: Analysis of biomarker kinetics (PSP, routine markers) was performed on 90 patients admitted to the Zurich Burn Center between May 2015 and October 2018 with burns ≥15% total body surface area with regard to infection and sepsis (Sepsis-3) over a 14-day time course. RESULTS: PSP differentiated between sepsis, infection and sterile inflammation from day 3 onward with an area under the curve of up to 0.89 (P < 0.001), therefore, competing with procalcitonin (area under the curve = 0.86, P < 0.001). Compared to routine inflammatory biomarkers, only PSP demonstrated a significant interaction between time and presence of sepsis - signifying a steeper increase in PSP levels in septic patients as opposed to those exhibiting a nonseptic course (interaction P < 0.001). Event-related analysis demonstrated tripled PSP serum levels within 72 hours and doubled levels within 48 hours before a clinically apparent sepsis. CONCLUSION: PSP is able to differentiate between septic and nonseptic patients during acute burn care. Its steep rise up to 72 hours before clinically overt deterioration has the potential for physicians to timely initiate treatment with reduced mortality and costs.

Safety of enzymatic debridement in extensive burns larger than 15% total body surface area.

OBJECTIVES: Bromelain-based enzymatic debridement has emerged as an alternative to surgical eschar removal. Indications include partial thickness, mixed pattern, and full-thickness burns. Enzymatic debridement has been approved by the European Medicines Agency for treating burn wounds affecting <15% total body surface area (TBSA). Data and evidence for the treatment of areas >15% TBSA in one session is scarce. The aim of this retrospective study was to retrospectively analyze off-label use of enzymatic debridement in a single burn center for large TBSA burns. METHODS: Between 01/2017 and 12/2018, 59 patients with partial- to full-thickness burns underwent enzymatic debridement in a single center study. Patients were categorized into two groups: the regular use group with a treated area less than 15% TBSA and the off-label group (OG) with larger TBSA debrided in one session. Treatment was evaluated for systemic inflammatory reaction, bleeding, hemodynamic instability and electrolyte shifts. RESULTS: In total, 49 patients were treated in the regular use group with a median application area of 6% (IQR 2.5-9.5) and 10 patients were treated in the off-label group with a median application area of 18% (IQR 15-19) TBSA. We found no significant differences regarding blood pressure, body temperature or hemodynamic stability during and after enzymatic debridement. No treatment-related serious adverse events were observed in either group. Catecholamine use was similar in both groups. No differences in leukocyte counts, CRP, PCT and lactate prior to application and during the following three days were observed. Sodium, potassium, chloride and phosphate levels did not differ. We found no evidence of an electrolyte shift. Survival was 49 of 49 patients (100%) in the RG and 7 of 10 patients (70%) in the OG (p = 0.004). CONCLUSION: Enzymatic debridement did not result in any expected or unexpected side effects in the patient groups investigated. These preliminary results indicate the potential safety of bromelain-based enzymatic debridementin the treatment of burns greater than 15% TBSA.

Sedation for magnetic resonance imaging using propofol with or without ketamine at induction in pediatrics-A prospective randomized double-blinded study.

INTRODUCTION: Deep sedation using propofol has become a standard technique in children. This double-blinded randomized clinical trial aims to compare the clinical effects of propofol-mono-sedation vs a combination of propofol and ketamine at induction and a reduced propofol infusion rate for maintenance in children undergoing diagnostic magnetic resonance imaging. METHODS: Children aged from 3 months to 10 years scheduled as outpatients for elective magnetic resonance imaging with deep sedation were included. They were randomized into 2 groups, receiving either 1 mg/kg ketamine at induction, then a propofol infusion rate of 5 mg/kg/h or a propofol infusion rate of 10 mg/kg/h without prior ketamine. Time to full recovery (modified Aldrete score = 10) was the primary outcome. Further outcomes were quality of induction, immobilization during image acquisition, recovery, postoperative nausea and vomiting, emergence delirium using the Pediatric Anesthesia Emergence Delirium scale, vital signs and adverse cardiorespiratory events. All patients and parents as well as anesthetists, imaging technicians, and postsedation personnel were blinded. Data are given as median (range). RESULTS: In total, 347 children aged 4.0 (0.25-10.9) years, weighing 15.6 (5.3-54) kg, ASA classification I, II, or III (141/188/18) were included. The ketamine-propofol group showed significantly shorter recovery times (38 (22-65) vs 54 (37-77) minutes; median difference 14 (95% CI: 8, 20) minutes; P < .001), better quality of induction, and higher blood pressure, but higher incidence of movement requiring additional sedative drugs. There were no significant differences in respiratory side effects, cardiovascular compromise, emergence delirium, or postoperative nausea and vomiting. CONCLUSION: Both sedation concepts proved to be reliable with a low incidence of side effects. Ketamine at induction with a reduced propofol infusion rate leads to faster postanesthetic recovery.

Sex-dependent differences in the in vivo respiratory phenotype of the TASK-1 potassium channel knockout mouse.

TASK-1 potassium channels have been implicated in central and peripheral chemoreception; however, the precise contribution of TASK-1 for the control of respiration is still under debate. Here, we investigated the respiration of unrestrained adult and neonatal TASK-1 knockout mice (TASK-1-/-) using a plethysmographic device. Respiration in adult female TASK-1-/- mice under control (21% O2), hypoxia and hypercapnia was unaffected. Under acute hypoxia male TASK-1-/- mice exhibited a reduced increase of the respiratory frequency (fR) compared to wildtypes. However, the tidal volume (VT) of male TASK-1-/- mice was strongly enhanced. The volatile anesthetic isoflurane induced in male TASK-1-/- and male wild type mice (TASK-1+/+) a similar respiratory depression. Neonatal TASK-1-/- mice demonstrated a 30-40% decrease of the minute volume, caused by a reduction of the fR under control condition (21% O2). Under hypoxia, neonatal TASK-1-/- mice more frequently stopped breathing (apnea>3s) suggesting an increased hypoxia-sensitivity. As reported before, this increased hypoxia sensitivity had no influence on the survival rate of neonatal TASK-1-/- mice. In adult and neonatal mice, TASK-1 gene deletion induced a significant prolongation of the relaxation time (RT), which is a parameter for expiration kinetics. Additionally, screening for mutations in the human TASK-1 gene in 155 cases of sudden infant death syndrome (SIDS) was inconclusive. In conclusion, these data are suggestive for an increased hypoxia-sensitivity of neonatal TASK-1-/- mice, however, without causing an increase in neonatal lethality. In adult female TASK-1-/- mice respiration was unaffected, whereas adult male TASK-1-/- mice showed a modified breathing pattern. These results are suggestive for sex-specific mechanisms for compensating the inactivation of TASK-1 in mice.