Absorption pharmacokinetics and feasibility of intranasal dexmedetomidine in patients under general anaesthesia.

BACKGROUND: The use of intranasal dexmedetomidine is hampered by a limited understanding of its absorption pharmacokinetics. METHODS: We examined the pharmacokinetics and feasibility of intranasal dexmedetomidine administered in the supine position to adult patients undergoing general anaesthesia. Twenty-eight patients between 35 and 80 years of age, ASA 1-3 and weight between 50 and 100 kg, who underwent elective unilateral total hip or knee arthroplasty under general anaesthesia were recruited. All patients received 100 µg of intranasal dexmedetomidine after anaesthesia induction. Six venous blood samples (at 0, 5, 15, 45, 60, 240 min timepoints from dexmedetomidine administration) were collected from each patient and dexmedetomidine plasma concentrations were measured. Concentration-time profiles after nasal administration were pooled with earlier data from a population analysis of intravenous dexmedetomidine (n = 202) in order to estimate absorption parameters using nonlinear mixed effects. Peak concentration (CMAX) and time (TMAX) were estimated using simulation (n = 1000) with parameter estimates and their associated variability. RESULTS: There were 28 adult patients with a mean (SD) age of 66 (8) years and weight of 83 (10) kg. The mean weight-adjusted dose of dexmedetomidine was 1.22 (0.15) µg kg-1. CMAX 0.273 µg L-1 was achieved at 98 min after intranasal administration (TMAX). The relative bioavailability of dexmedetomidine was 80% (95% CI 75-91%). The absorption half-time (TABS = 120 min; 95% CI 90-147 min) was slower than that in previous pharmacokinetic studies on adult patients. Perioperative haemodynamics of all patients remained stable. CONCLUSIONS: Administration of intranasal dexmedetomidine in the supine position during general anaesthesia is feasible with good bioavailability. This administration method has slower absorption when compared to awake patients in upright position, with consequent concentrations attained after TMAX for several hours.

Furosemide versus placebo for fluid overload in intensive care patients-The randomised GODIF trial second version: Statistical analysis plan.

BACKGROUND: Fluid overload is associated with increased mortality in intensive care unit (ICU) patients. The GODIF trial aims to assess the benefits and harms of fluid removal with furosemide versus placebo in stable adult patients with moderate to severe fluid overload in the ICU. This article describes the detailed statistical analysis plan for the primary results of the second version of the GODIF trial. METHODS: The GODIF trial is an international, multi-centre, randomised, stratified, blinded, parallel-group, pragmatic clinical trial, allocating 1000 adult ICU patients with moderate to severe fluid overload 1:1 to furosemide versus placebo. The primary outcome is days alive and out of hospital within 90 days post-randomisation. With a power of 90% and an alpha level of 5%, we may reject or detect an improvement of 8%. The primary analyses of all outcomes will be performed in the intention-to-treat population. For the primary outcome, the Kryger Jensen and Lange method will be used to compare the two treatment groups adjusted for stratification variables supplemented with sensitivity analyses in the per-protocol population and with further adjustments for prognostic variables. Secondary outcomes will be analysed with multiple linear regressions, logistic regressions or the Kryger Jensen and Lange method as suitable with adjustment for stratification variables. CONCLUSION: The GODIF trial data will increase the certainty about the effects of fluid removal using furosemide in adult ICU patients with fluid overload. TRIAL REGISTRATIONS: EudraCT identifier: 2019-004292-40 and ClinicalTrials.org: NCT04180397.

New-onset atrial fibrillation in critically ill acute kidney injury patients on renal replacement therapy.

AIMS: The effect of new-onset atrial fibrillation (NOAF) on mortality in critically ill patients with acute kidney injury (AKI) treated in the intensive care unit (ICU) requiring continuous veno-venous haemodialysis (CVVHD) or intermittent haemodialysis (IHD) is unknown. Thus, we examined the incidence of NOAF in critically ill AKI patients undergoing CVVHD or IHD and the association between the timing of NOAF incidence in relation to renal replacement therapy (RRT) initiation and 1-year mortality. METHODS AND RESULTS: Out of the 733 consecutively recruited ICU patients requiring RRT within the study period of 2010-2019, 516 patients without prior atrial fibrillation history were included in this retrospective study. Clinical comorbidities, medications and biochemistry as well as outcome data for 1-year all-cause mortality were recorded. Episodes of NOAF were collected from the pooled rhythm data covering the entire ICU stay of every patient. The median age was 64 (inter-quartile range 19) years, 165 (32%) were female, and 356 and 160 patients received CVVHD and IHD, respectively. NOAF was observed in 190 (37%) patients during ICU care and 217 (42%) patients died within the 1-year follow-up. Incident NOAF was independently associated with 1-year mortality in the multivariable logistic regression analysis after adjusting for dialysis modality, need for mechanical ventilation or vasopressor support and Acute Physiology And Chronic Health Evaluation II score. However, NOAF diagnosed after RRT initiation was not associated with mortality. CONCLUSION: NOAF emerging before RRT initiation is associated with increased mortality in critically ill AKI patients requiring RRT. However, NOAF during RRT does not seem to be associated with mortality.

Hemodynamic and respiratory effects of dexmedetomidine sedation in critically ill Covid-19 patients: A retrospective cohort study.

INTRODUCTION: Dexmedetomidine has been suggested to be a promising sedative for patients with Covid-19 infection (CV19). However, use of dexmedetomidine is limited by its heart rate (HR) and arterial blood pressure lowering effects. Moreover, CV19 is associated with cardiac manifestations including bradyarrythmias. The hemodynamic effects of dexmedetomidine have not been previously studied in CV19 patients. We evaluated the effects of dexmedetomidine on hemodynamic and respiratory parameters of CV19 patients. METHODS: In this single center study, all CV19 patients receiving dexmedetomidine for sedation during a one year period were included. Our primary outcomes included changes in HR, mean arterial pressure (MAP), respiratory rate (RR), partial oxygen pressure of arterial blood/fraction of inspired oxygen-ratio (PF-ratio), and Richmond Agitation and Sedation Score (RASS) during dexmedetomidine administration. RESULTS: We identified 39 patients with a mean (SD) age of 58.3 (12.7) years. After initiation of dexmedetomidine, HR decreased by 16.9 (3.3) beats/min (95% CI 9.5-22.4; p < 0.001). During the 12-hour follow-up period, HR decrease was significant at 2 to 12 h. Incident bradycardia (<45/min) was reported in 12 (30.8%) patients and it was associated with lower plasma C-reactive protein, Pro-calcitonin, and troponin T levels. There was no change in MAP compared to baseline. Dexmedetomidine administration was associated with improvement of PF-ratio (p < 0.001) and with decrease of RASS (p = 0.004). CONCLUSIONS: Dexmedetomidine is an effective sedative for CV19 patients and may improve their oxygenation. However, dexmedetomidine administration is associated with marked decline in HR and with a high incidence of bradycardia in patients with CV19.

Continuous hemodialysis with citrate anticoagulation and standard dialysate for managing acute kidney injury in patients with moderate to severe hyponatremia-A retrospective study.

BACKGROUND: The safety of continuous veno-venous hemodialysis (CVVHD) with citrate-calcium anticoagulation for acute kidney injury (AKI) with coincident hyponatremia remains unclear. We aimed to explore the feasibility of CVVHD with standard dialysate and citrate-calcium anticoagulation in hyponatremic critically ill AKI patients. METHODS: Thirty-seven of the 493 critically ill AKI patients requiring CVVHD and admitted to our intensive care unit during a 10-year period had hyponatremia (<130 mmol/L) and were included in this retrospective study. All patients received CVVHD with citrate-calcium anticoagulation and standard commercial dialysate and plasma sodium concentrations were frequently controlled until death or CVVHD discontinuation. Clinical data, mortalities and cases of central pontine myelinolysis within one-year follow-up were recorded. RESULTS: Median plasma sodium concentration was 127 (IQR 124-129) mmol/L at CVVHD initiation. CVVHD duration was median 3 (IQR 1.5-5.5) days and the mean daily sodium load of the trisodium citrate solution during the first 3 days of CVVHD was 1754 (SD 730) mmol. The plasma sodium concentration increased a median 8 (IQR 5-10) mmol/L during the first 24 hours of CVVHD and excessively high plasma sodium correction (>8 mmol/L/24 h) was observed in 18 (48.6%) patients. However, increased mortality in association to rapid plasma sodium correction was not observed in this study. CONCLUSIONS: CVVHD using standard citrate-calcium anticoagulation effectively increased plasma sodium concentration in this study. However, excessively high plasma sodium correction was observed in half of the patients and the sodium load provided by the standard citrate anticoagulation solutions was substantial.

Intranasal Dexmedetomidine Reduces Postoperative Opioid Requirement in Patients Undergoing Total Knee Arthroplasty Under General Anesthesia.

BACKGROUND: Total knee arthroplasty (TKA) causes severe pain, and strong opioids are commonly used in postoperative analgesia. Dexmedetomidine is a novel alpha-2-adrenoceptor-activating drug indicated for procedural sedation, but previous studies have shown clinically relevant analgesic and antiemetic effects. We evaluated retrospectively the effect of intranasal dexmedetomidine on the postoperative opioid requirement in patients undergoing TKA. METHODS: One hundred and fifty patients with ASA status 1-2, age between 35 and 80 years, and scheduled for unilateral primary TKA under total intravenous anesthesia were included in the study. Half of the patients received 100 µg of intranasal dexmedetomidine after anesthesia induction, while the rest were treated conventionally. The postoperative opioid requirement was calculated as morphine equivalent doses for both groups. The effect of dexmedetomidine on postoperative hemodynamics, length of stay (LOS), and incidence of postoperative nausea and vomiting (PONV), was evaluated. RESULTS: The cumulative postoperative opioid consumption was significantly reduced in the dexmedetomidine group compared to the control group (-28.5 mg, 95% CI 12-47 mg P < .001). The reduction in cumulative opioid dose was significantly different between the groups already at 2, 12, 24, and 36 h postoperatively (P < .001). LOS was shorter in the dexmedetomidine group (P < .001), and the dexmedetomidine group had lower postoperative mean arterial pressure and heart rates were lower compared to the control group (P < .001). The incidence of PONV did not differ between the groups (P = .64). CONCLUSION: Intraoperatively administered intranasal dexmedetomidine reduces postoperative opioid consumption and may be associated with a shorter hospital stay in patients undergoing TKA under general anesthesia.

Renal Replacement Techniques in Septic Shock.

Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to an infection; it carries a risk for mortality, considerably exceeding that of a mere infection. Sepsis is the leading cause for acute kidney injury (AKI) and the requirement for renal replacement therapy (RRT) in intensive care unit (ICU) patients. Almost every second critically ill patient with sepsis will develop AKI. In septic shock, the dysregulated host response to infectious pathogens leads to a cytokine storm with uncontrolled production and release of humoral proinflammatory mediators that evoke cellular toxicity and promote the development of organ dysfunction and increased mortality. In addition to treating AKI, RRT techniques can be employed for extracorporeal adsorption of inflammatory mediators using specifically developed adsorption membranes, hemoperfusion sorbent cartridges or columns; these techniques are intended to decrease the level and early deleterious effects of circulating proinflammatory cytokines and endotoxins during the first hours and days of septic shock treatment, in order to improve patient outcomes. Several methods and devices, such as high cut-off membranes, the Oxiris®-AN69 membrane, CytoSorb® and HA380 cytokine hemoadsorption, polymyxin B endotoxin adsorption, and plasmapheresis have been examined in small study series or are under evaluation as ways of improving patient outcomes in septic shock. However, to date, the data on actual outcome benefits have remained controversial, as discussed in this review.

Pharmacokinetics and Sedative Effects of Intranasal Dexmedetomidine in Ambulatory Pediatric Patients.

BACKGROUND: Our aim was to characterize the pharmacokinetics and sedative effects of intranasally (IN) administered dexmedetomidine used as an adjuvant in pediatric patients scheduled for magnetic resonance imaging (MRI) requiring sedation. METHODS: This was an open-label, single-period study without randomization. Pediatric patients from 5 months to 11 years of age scheduled for MRI and receiving IN dexmedetomidine for premedication as part of their care were included in this clinical trial. Single doses of 2-3 µg·kg of dexmedetomidine were applied IN approximately 1 hour before MRI. Five or 6 venous blood samples were collected over 4 hours for dexmedetomidine concentration analysis. Sedation was monitored with Comfort-B scores, and vital signs were recorded. Pharmacokinetic variables were calculated with noncompartmental methods and compared between 3 age groups (between 1 and 24 months, from 24 months to 6 years, and over 6-11 years). RESULTS: We evaluated 187 consecutive patients for suitability, of which 132 were excluded. Remaining 55 patients were recruited, of which 5 were excluded before the analysis. Data from 50 patients were analyzed. The average (standard deviation [SD]) dose-corrected peak plasma concentration (Cmax) was 0.011 liter (0.0051), and the median (interquartile range [IQR]) time to reach peak concentration (tmax) was 37 minutes (30-45 minutes). There was negative correlation with Cmax versus age (r = -0.58; 95% confidence interval [CI], -0.74 to -0.37; P < .001), but not with tmax (r = -0.14; 95% CI, 0.14-0.39; P = .35). Dose-corrected areas under the concentration-time curve were negatively correlated with age (r = -0.53; 95% CI, 0.70 to -0.29; P < .001). Median (IQR) maximal reduction in Comfort-B sedation scores was 8 (6-9), which was achieved 45 minutes (40-48 minutes) after dosing. Median (IQR) decrease in heart rate was 15% (9%-23%) from the baseline. CONCLUSIONS: Dexmedetomidine is relatively rapidly absorbed after IN administration and provides clinically meaningful but short-lasting sedation in pediatric patients.

Mortality and renal prognosis in isolated metformin-associated lactic acidosis treated with continuous renal replacement therapy and citrate-calcium-anticoagulation.

INTRODUCTION: Use of metformin increases plasma lactate concentration and may lead to metformin-associated lactic acidosis (MALA). Previous studies have suggested severe MALA to have a mortality of 17%-21%, but have included patients with other coincident conditions such as sepsis. The treatment of choice is continuous renal replacement therapy (CRRT), which has been performed using heparin analogues or no anticoagulation in former studies. MATERIALS AND METHODS: Patients admitted to the Intensive Care Unit of Turku University Hospital Finland with lactic acidosis without any other recognizable etiology than concomitant metformin treatment who required CRRT between years 2010 and 2019 were included. CRRT was performed using regional citrate-calcium-anticoagulation. Data extracted included patient demographics, comorbidities, and clinical parameters at 6-hour intervals about 72 hours from admission. Creatinine and estimated glomerular filtration rate (eGFR) were measured at 1 year after MALA. RESULTS: A total of 23 patients with isolated MALA were included in the study. Median (IQR) pH was 6.88 (6.81-7.07) and lactate 16.1 (11.9-23.0) mmol/L on admission. Median (IQR) duration of CRRT was 62 (41-70) hours. Seven patients (30%) required mechanical ventilation with a mean duration of 6.0 ± 3.0 days. 90-day mortality was 4.3% and 1-year mortality 13.0%. Creatinine (P = .02) and eGFR (P = .03) remained significantly altered at 1 year of follow-up compared to baseline. CONCLUSIONS: MALA can be treated effectively and safely with CRRT and citrate-calcium-anticoagulation, usually required for 2-3 days. Mortality of patients with MALA treated with CRRT is low when other conditions inducing lactic acidosis are excluded. MALA episode may be associated with long-lasting kidney injury.

Markers of Poor Prognosis in Patients Requiring Continuous Renal Replacement Therapy After Cardiac Surgery.

OBJECTIVE: Acute kidney injury requiring renal replacement therapy after cardiac surgery has an incidence of 2% to 15%, and mortality in affected patients approximates 50%. The authors aimed to study the determinants of poor prognosis in patients receiving continuous renal replacement therapy (CRRT) after cardiac surgery. DESIGN: Retrospective, observational single-center study. SETTING: Tertiary care, university hospital. PARTICIPANTS: Cardiac surgery patients admitted to the intensive care unit (ICU) needing postoperative CRRT between January 1, 2010, and September 31, 2019. INTERVENTIONS: Predictors of mortality were examined using groupwide comparisons between ICU survivors versus nonsurvivors and univariate and multivariate Cox proportional hazards models. RESULTS: During the study period, 67 cardiac surgery patients without prior maintenance dialysis required CRRT postoperatively. ICU mortality was 47.7% and 90-day mortality was 58.2%. Only 37.3% of patients were alive at 1 year after surgery. Blood lactate at the start of dialysis was the most significant predictor of ICU and overall mortality. Eighty-seven percent of patients with lactate >3 mmol/L died in the ICU compared with 27.3% of patients with lactate ≤3 mmol/L (p < 0.0001). In patients with lactate exceeding 5.3 mmol/L, ICU mortality was 100%. In a stepwise multivariate Cox proportional hazards model, the association with mortality remained significant for lactate at the start of CRRT (per 1 mmol/L, hazard ratio [HR] 1.19 [95% confidence interval {CI} 1.11-1.28], p < 0.0001), troponin T on the first postoperative morning (per 0.1 µg/L, HR 1.004 [95% CI 1.001-1.008], p = 0.01), and 72-hour fluid balance (per 1000 mL, HR 1.12 [95% CI 1.04-1.21], p = 0.005). CONCLUSION: Blood lactate at the start of dialysis was the most significant predictor of ICU and overall mortality in patients with CRRT after cardiac surgery.

Premedication with intranasal dexmedetomidine decreases barbiturate requirement in pediatric patients sedated for magnetic resonance imaging: a retrospective study.

BACKGROUND: Barbiturates are commonly used in ambulatory sedation of pediatric patients. However, use of barbiturates involve risks of respiratory complications. Dexmedetomidine, a highly selective α2-adrenoceptor agonist, is increasingly used for pediatric sedation. Premedication with intranasal (IN) dexmedetomidine offers a non-invasive and efficient possibility to sedate pediatric patients undergoing magnetic resonance imaging (MRI). Our hypothesis was that dexmedetomidine would reduce barbiturate requirements in procedural sedation. METHODS: We included 200 consecutive pediatric patients undergoing MRI, and analyzed their hospital records retrospectively. Half of the patients received 3 µg/kg of IN dexmedetomidine (DEX group) 45-60 min before MRI while the rest received only thiopental (THIO group) for procedural sedation. Sedation was maintained with further intravenous thiopental dosing as needed. Thiopental consumption, heart rate (HR) and peripheral oxygen saturation were recorded. RESULTS: The cumulative thiopental requirement during MRI was (median and interquartile range [IQR]) 4.4 (2.7-6.0) mg/kg/h in the DEX group and 12.4 (9.8-14.8) mg/kg/h in the THIO group (difference 7.9 mg/kg/h, 95% CI 6.8-8.8, P <  0.001). Lowest measured peripheral oxygen saturation remained slightly higher in the DEX group compared to the THIO group (median nadirs and IQR: 97 (95-97) % and 96 (94-97) %, P <  0.001). Supplemental oxygen was delivered to 33% of the patients in the THIO group compared to 2% in the DEX group (P <  0.001). The lowest measured HR (mean and SD) was lower (78 (16) bpm) in the DEX group compared to the THIO group (92 (12) bpm) (P <  0.001). CONCLUSION: Premedication with IN dexmedetomidine (3 µg/kg) was associated with markedly reduced thiopental dosage needed for efficient procedural sedation for pediatric MRI.

Intranasal Low-Dose Dexmedetomidine Reduces Postoperative Opioid Requirement in Patients Undergoing Hip Arthroplasty Under General Anesthesia.

BACKGROUND: Patients undergoing total hip arthroplasty (THA) need substantial amount of opioids for postoperative pain management, which necessitates opioid-sparing modalities. Dexmedetomidine is a novel alpha-2-adrenoceptor-activating drug for procedural sedation. In addition to its sedative effect, dexmedetomidine has analgesic and antiemetic effects. We evaluated retrospectively the effect of intraoperatively administered intranasal low-dose dexmedetomidine on postoperative opioid requirement in patients undergoing THA. METHODS: We included 120 patients with American Society of Anesthesiologists status 1-2, age between 35 and 80 years, and scheduled for unilateral primary THA under general anesthesia with total intravenous anesthesia. Half of the patients received 50 µg of intranasal dexmedetomidine after anesthesia induction, while the rest were treated conventionally. Postoperative opioid requirements were calculated as morphine equivalent doses for both groups. The impact of intranasal dexmedetomidine on postoperative hemodynamics and length of stay was evaluated. RESULTS: The cumulative postoperative opioid requirement was significantly reduced in the dexmedetomidine group compared with the control group (26.3 mg, 95% confidence interval 15.6-36.4, P < .001). The cumulative dose was significantly different between the groups already at 12, 24, and 36 h postoperatively (P = .01; P = .001; P < .001, respectively). Dexmedetomidine group had lower mean arterial pressure in the postanesthesia care unit compared with the control group (P = .01). There was no difference in the postanesthesia care unit stay or postoperative length of stay between the two groups (P = .47; P = .10, respectively). CONCLUSION: Compared with the control group, intraoperative use of intranasal low-dose dexmedetomidine decreases opioid consumption and sympathetic response during acute postoperative period in patients undergoing THA.

A case report of an accidental iatrogenic dexmedetomidine overdose in an adult.

BACKGROUND: Dexmedetomidine is a sedative drug with a wide safety margin. CASE PRESENTATION: We present a case of accidental iatrogenic dexmedetomidine overdose in an adult patient during high-intensity focused ultrasound (HIFU) treatment. This is the first case report of an adult patient receiving an intravenous push of dexmedetomidine. Overdose resulted in severe oversedation, but symptoms receded spontaneously over time. CONCLUSIONS: Dexmedetomidine overdoses are infrequent, and they are usually the result of an administration error.

Chloride, Sodium and Calcium Intake Are Associated with Mortality and Follow-Up Kidney Function in Critically Ill Patients Receiving Continuous Veno-Venous Hemodialysis-A Retrospective Study.

BACKGROUND: Studies on the association between solute, nutrition and fluid intakes and mortality and later kidney function in critically ill acute kidney injury (AKI) patients receiving continuous veno-venous hemodialysis (CVVHD) are scarce. METHODS: Altogether, 471 consecutive critically ill AKI patients receiving CVVHD in the research intensive care unit (ICU) were recruited in this single-center, retrospective study. RESULTS: The median age was 66 (58-74) years, and 138 (29.3%) were female. The 90-day and one-year mortalities were 221 (46.9%) and 251 (53.3%), respectively. After adjusting for age, sex, Acute Physiology and Chronic Health Evaluation II (APACHE) score, coronary artery disease, immunosuppression, ICU care duration, mechanical ventilation requirement, vasopressor requirement and study time period, the cumulative daily intake of potassium, chloride, sodium, phosphate, calcium, glucose, lipids and water was associated with one-year mortality in separate multivariable cox proportional hazards models. In a sensitivity analysis excluding patients who died within the first three days of ICU care, the daily intake of chloride (hazard ratio (HR) 1.001, confidence interval (CI) 95% 1.000-1.003, p = 0.032), sodium (HR 1.001, CI 95% 1.000-1.002, p = 0.031) and calcium (HR 1.129, CI 95% 1.025-1.243, p = 0.014) remained independently associated with mortality within one-year in the respective, similarly adjusted multivariable cox analyses. The cumulative daily intake of chloride, sodium, calcium and water was independently associated with the estimated glomerular filtration rate (eGFR) at 90 days follow-up in separate substantially adjusted multivariable cox proportional hazards models. CONCLUSION: The cumulative daily intake of chloride, sodium and calcium is associated with mortality and daily chloride, sodium, calcium and water intake is associated with follow-up eGFR in critically ill patients with CVVHD-treated AKI.

Pre-emptive vs. classic criteria for initiation of dialysis in critically ill patients with acute kidney injury (AKI) - A retrospective real-world study.

INTRODUCTION: Guidelines recommend starting renal replacement therapy (RRT) in critically ill acute kidney injury (AKI) patients according to classic criteria for the initiation of dialysis (CCID). However, comparative data on the presence or absence of CCID in patients receiving continuous veno-venous hemodialysis (CVVHD) or intermittent hemodialysis (IHD) as the initial modality are scarce. METHODS: Altogether 733 critically ill AKI patients receiving CVVHD or IHD at the research hospital between 2010 and 2019 were screened for this real-world study. All patients on maintenance dialysis were excluded. Patient survival was studied in 662 patients and adverse renal outcomes in 375 surviving patients at 90 days follow-up. The adverse renal outcome was defined as RRT requirement and the secondary outcome was estimated glomerular filtration rate (eGFR) at 90 days follow-up. FINDINGS: Altogether 472 (71.3%) patients received CVVHD and 190 (28.7%) IHD, and CCID was present at the time of RRT initiation in 250 (37.8%). The CCID was independently associated with mortality in a multivariable logistic regression analysis (odds ratio [OR] 2.226, 95% confidence interval [CI] 1.455-3.407, p < 0.001) adjusted for age, sex, baseline eGFR, disease severity, RRT modality, hypertension, and diabetes. The presence of CCID at the start of RRT was not associated with adverse renal outcome (OR 0.548, 95% CI 0.230-1.305, p = 1.74) nor eGFR (ß = 0.155, p = 0.066) at 90 days follow-up. However, starting RRT in the presence of CCID was independently associated with eGFR at 90 days follow-up in a multivariable ordinal regression analysis (ß = 0.930, p = 0.018) after adjusting for age, sex, baseline eGFR, disease severity markers, hypertension, and diabetes in patients receiving CVVHD but not IHD as the initial modality. DISCUSSION: The presence of CCID at the initiation of RRT was associated with mortality but not adverse renal outcomes in this large real-world study on critically ill AKI patients requiring RRT. Initiating RRT in the presence of CCID was associated with improved eGFR at 90 days follow-up in patients receiving CVVHD as the initial modality.

Scarpa Fascia Preservation to Reduce Seroma Rate on Massive Weight Loss Patients Undergoing Abdominoplasty: A Comparative Study.

(1) Background: An increasing number of patients undergo bariatric surgery and seek body contouring surgery after massive weight loss (MWL). Abdominoplasty itself is associated with a high complication rate in these patients, particularly due to seroma formation. Scarpa fascia preservation (SFP) has been proven to be an efficient method of reducing seroma rates. We aimed to evaluate the possible benefits of SFP on massive weight loss patients comparatively. (2) Methods: This is a single-center retrospective comparative study encompassing 202 MWL patients operated between 2009 and 2019 at Turku University Hospital. Patients included in the study had a preoperative weight loss greater than 30 kg. Of them, 149 went through traditional abdominoplasty and 53 abdominoplasties with SFP. The primary outcome measure was seroma occurrence, while secondary outcomes included drainage amount, hospital stay, surgical site occurrence, and need for blood transfusion. (3) Results: The only statistically significant difference between groups on patients' demographics was the sex ratio, favoring females in the control group (43:10, 81% vs. 130:19, 87%, p = 0.018). SFP significantly reduced seroma occurrence (9.4% vs. 26.2%, p = 0.011) and decreased mean drainage duration (3.7 ± 2.4 vs. 5.3 ± 3.2 days, p = 0.025). There was a trend towards lower drainage output (214.1 ± 162.2 mL vs. 341.9 ± 480.5 mL, p = 0.060) and fewer postoperative days on ward in the SFP group. Other complication incidences did not differ between the groups. The multivariable analysis did not show any significant factor for seroma formation or surgical site occurrence. (4) Conclusions: Preserving Scarpa fascia on MWL patients may result in decreased seroma occurrence and a shorter time to drain removal.

Predicting mortality in critically ill patients requiring renal replacement therapy for acute kidney injury in a retrospective single-center study of two cohorts.

Half of the critically ill patients with renal replacement therapy (RRT) dependent acute kidney injury (AKI) die within one year despite RRT. General intensive care prediction models perform inadequately in AKI. Predictive models for mortality would be an invaluable complementary tool to aid clinical decision making. We aimed to develop and validate new prediction models for intensive care unit (ICU) and hospital mortality customized for patients with RRT dependent AKI in a retrospective single-center study. The models were first developed in a cohort of 471 critically ill patients with continuous RRT (CRRT) and then validated in a cohort of 193 critically ill patients with intermittent hemodialysis (IHD) as the primary modality for RRT. Forty-two risk factors for mortality were examined at ICU admission and CRRT initiation, respectively, in the first univariate models followed by multivariable model development. Receiver operating characteristics curve analyses were conducted to estimate the area under the curve (AUC), to measure discriminative capacity of the models for mortality. AUCs of the respective models ranged between 0.76 and 0.83 in the CRRT model development cohort, thereby showing acceptable to excellent predictive power for the mortality events (ICU mortality and hospital mortality). The models showed acceptable external validity in a validation cohort of IHD patients. In the IHD validation cohort the AUCs of the MALEDICT RRT initiation model were 0.74 and 0.77 for ICU and hospital mortality, respectively. The MALEDICT model shows promise for mortality prediction in critically ill patients with RRT dependent AKI. After further validation, the model might serve as an additional clinical tool for estimating individual mortality risk at the time of RRT initiation.

Mortality and associated risk factors in patients with severe methanol or ethylene glycol poisoning treated with dialysis: a retrospective cohort study.

OBJECTIVE: To compare the initial clinical course and data on 90-day mortality in adults with methanol (MET) or ethylene glycol (EG) poisoning treated with dialysis. METHODS: Data on patient demographics and clinical parameters at intensive care unit (ICU) admission and for the first 24 hours after dialysis initiation were collected, and 90-day outcome data were collected for patients with MET (n = 15) or EG (n = 13) poisoning treated with dialysis in this retrospective cohort study. RESULTS: In univariate analysis, patients with EG poisoning were older and they had lower hourly urine output during the first 24 hours after the initiation of dialysis. Six (46%) patients with MET poisoning and three (20%) patients with EG poisoning died within 90 days of ICU admission. A larger anion gap and lower pH, bicarbonate levels, base excess, and Glasgow Coma Scale scores on admission, as well as the need for mechanical ventilation, were associated with 90-day mortality. CONCLUSIONS: Metabolic acidosis, a large anion gap, and an altered mental status on admission appear to be associated with mortality in MET or EG poisoning, and EG poisoning may be linked to lower urine output.

Could dexmedetomidine be repurposed as a glymphatic enhancer?

Cerebrospinal fluid (CSF) flows through the central nervous system (CNS) via the glymphatic pathway to clear the interstitium of metabolic waste. In preclinical studies, glymphatic fluid flow rate increases with low central noradrenergic tone and slow-wave activity during natural sleep and general anesthesia. By contrast, sleep deprivation reduces glymphatic clearance and leads to intracerebral accumulation of metabolic waste, suggesting an underlying mechanism linking sleep disturbances with neurodegenerative diseases. The selective α2-adrenergic agonist dexmedetomidine is a sedative drug that induces slow waves in the electroencephalogram, suppresses central noradrenergic tone, and preserves glymphatic outflow. As recently developed dexmedetomidine formulations enable self-administration, we suggest that dexmedetomidine could serve as a sedative-hypnotic drug to enhance clearance of harmful waste from the brain of those vulnerable to neurodegeneration.