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.

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.

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.

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.

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.

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.

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.

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.

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.

Mortality and associated risk factors in perioperative acute kidney injury treated with continuous renal replacement therapy.

BACKGROUND: Perioperative acute kidney injury (AKI) is associated with multiple postoperative complications leading to prolonged hospital stay and higher costs. AKI requiring continuous renal replacement therapy (CRRT) after surgery has an incidence of 2-6% and mortality approximates 40-60%. Previous studies examining mortality in perioperative AKI patients managed with CRRT have concentrated on cardiac surgery patients and there are very limited data on broad surgical patient populations requiring CRRT. We examined long-term mortality and factors associated with poor outcome in a broad surgical population requiring CRRT for perioperative AKI during a 10-year period. METHODS: Surgical patients admitted to the intensive care unit (ICU) of academic tertiary hospital requiring CRRT between years 2010-2019 were included. CRRT was performed using regional citrate-calcium-anticoagulation. Extracted data included patient demographics, comorbidities, and clinical parameters at ICU admission and at the initiation of CRRT. Creatinine and estimated glomerular filtration rate (eGFR) were measured at 1 year after ICU admission. RESULTS: A total of 157 patients were included in the study. ICU mortality was 42.7%, 90-day mortality 58.0% and 1-year mortality 62.4%. Blood lactate at ICU admission and CRRT initiation were independently associated with mortality in the multivariate models. Patients with lactate > 4 mmol/l had higher mortality than patients with normal lactate (77% vs. 21%) (p < 0.001). Creatinine (p = 0.004) and eGFR (p < 0.001) remained significantly altered at 1 year of follow-up compared to baseline. CONCLUSIONS: Patients undergoing surgery and requiring perioperative CRRT in the ICU have a high risk of mortality. Mortality appears to be independently associated with lactate levels.

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.

Early restrictive fluid balance is associated with lower hospital mortality independent of acute disease severity in critically ill patients on CRRT.

Fluid overload (FO) with coincident acute kidney injury has been associated with increased mortality. However, it is unclear whether FO is an independent determinant of mortality for disease severity. We aimed to explore whether the development of fluid balance (FB) during the first 72 h of continuous renal replacement therapy (CRRT) is independently associated with hospital mortality. All patients admitted to a single centre ICU requiring CRRT for at least 24 h between years 2010-2019 were included. Extracted data included patient demographics and clinical parameters including daily cumulative fluid balance (FBcum), lactate, SOFA score and vasoactive requirement at the initiation and during the first 72 h of CRRT. 399 patients were included in the analysis. Hospital survivors had a significantly lower FBcum at CRRT initiation compared to non-survivors (median 1382 versus 3265 ml; p = 0.003). Hourly fluid balance per bodyweight (FBnet) was lower in survivors at 0-24, 24-48 and 48-72 h after initiation of CRRT (p < 0.008 for all comparisons). In the survival analysis (analyzed with counting process model) significant time-dependent explanatory variables for hospital mortality were FBnet (per ml/kg/h: HR: 1.319, 95% CI 1.038-1.677, p = 0.02), lactate (HR: 1.086, 95% CI 1.030-1.145, p = 0.002) and SOFA score (per ml/kg/h: HR: 1.084, 95% CI 1.025-1.146, p = 0.005) during the first 72 h of CRRT. Even after careful adjustment for repeated measures of disease severity, FBnet during the first 72 h of CRRT remains independently associated with hospital mortality, in critically ill patients with AKI.

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.

Mortality and associated risk factors in patients with blood culture positive sepsis and acute kidney injury requiring continuous renal replacement therapy-A retrospective study.

OBJECTIVES: Septic acute kidney injury (AKI) requiring continuous renal replacement therapy (CRRT) carries a mortality risk nearing 50%. Risk factors associated with mortality in AKI patients undergoing CRRT with blood culture positive sepsis remain unclear as sepsis has been defined according to consensus criteria in previous studies. METHODS: Risk factors associated with intensive care unit (ICU), 90-day and overall mortality were studied in a retrospective cohort of 126 patients with blood culture positive sepsis and coincident severe AKI requiring CRRT. Comprehensive laboratory and clinical data were gathered at ICU admission and CRRT initiation. RESULTS: 38 different causative pathogens for sepsis and associated AKI were identified. ICU mortality was 30%, 90-day mortality 45% and one-year mortality 50%. Immunosuppression, history of heart failure, APACHE II and SAPS II scores, C-reactive protein and lactate at CRRT initiation were independently associated with mortality in multivariable Cox proportional hazards models. Blood lactate showed good predictive power for ICU mortality in receiver operating characteristic curve analyses with AUCs of 0.76 (95%CI 0.66-0.85) for lactate at ICU admission and 0.84 (95%CI 0.72-0.95) at CRRT initiation. CONCLUSIONS: Our study shows for the first time that lactate measured at CRRT initiation is predictive of ICU mortality and independently associated with overall mortality in patients with blood culture positive sepsis and AKI requiring CRRT. Microbial etiology for septic AKI requiring CRRT is diverse.

Feasibility of Intranasal Dexmedetomidine in Treatment of Postoperative Restlessness, Agitation, and Pain in Geriatric Orthopedic Patients.

OBJECTIVE: The aim of this study was to report preliminary data on the use of intranasal dexmedetomidine to treat postoperative restlessness, agitation, and pain in 23 patients aged > 70 years and undergoing orthopedic surgery. BACKGROUND: Postoperative agitation and delirium are common among older adult patients undergoing orthopedic surgery. Most preparations used to treat agitation and delirium carry a risk for adverse events such as respiratory failure. Moreover, mere opioid therapy may be insufficient in treatment of pain. Dexmedetomidine, an α2-adrenoreceptor agonist with sedative and analgesic properties, has been shown to reduce opioid requirement and reduce postoperative delirium in older adults. METHODS: We studied the use of post-operative intranasal dexmedetomidine in a retrospective study cohort of geriatric patients undergoing orthopedic surgery. Primary outcomes included alterations in heart rate (HR), mean arterial pressure (MAP), respiratory rate (RR), peripheral oxygen saturation (SpO2), Modified Richmond Agitation and Sedation Score (mRASS), and opioid consumption following dexmedetomidine administration. RESULTS: We identified 23 patients with a mean (SD) age of 79.9 (7.5) years who received dexmedetomidine 100 µg intranasally postoperatively. After dexmedetomidine administration, HR decreased by 10.4 (3.7) beats/min (95% CI 2.9-17.8; p = 0.004) and MAP by 16.2 (4.4) mmHg (95% CI 7.3-25.1; p < 0.001). HR decrease was significant at 2 h and MAP decrease at 1, 2, and 3 h following dexmedetomidine administration. Dexmedetomidine administration was associated with significant reductions in opioid consumption (p < 0.001) and mRASS score (p < 0.001). SpO2 and RR remained unchanged. CONCLUSIONS: These preliminary findings suggest that intranasal dexmedetomidine reduces opioid consumption without causing respiratory depression and may be used to treat postoperative restlessness, agitation, and pain in geriatric patients. However, hemodynamic effects of dexmedetomidine may require close observation for 3 hours following administration in older adult patients.

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.

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.