Efficacy and safety of enteral supplementation with high-dose vitamin D in critically ill patients with vitamin D deficiency.

BACKGROUND: Vitamin D deficiency is associated with mortality and morbidity in critically ill patients. This study investigated the safety and effectiveness of enteral high-dose vitamin D supplementation in intensive care unit (ICU) patients in Asia. METHODS: This was a multicenter, prospective, randomized-controlled study. Eligible participants with vitamin D deficiency were randomly assigned to the control or vitamin D supplementation group. In the vitamin D supplementation group, the patients received 569,600 IU vitamin D. The primary outcome was the serum 25(OH)D level on day 7. RESULTS: 41 and 20 patients were included in the vitamin D supplementation and control groups, respectively. On day 7, the serum 25(OH)D level was significantly higher in the vitamin D supplementation group compared to the control group (28.5 [IQR: 20.2-52.6] ng/mL and 13.9 [IQR: 11.6-18.8] ng/mL, p < 0.001). Only 41.5% of the patients achieved serum 25(OH)D levels higher than 30 ng/mL in the supplementation group. This increased level was sustained in the supplementation group on both day 14 and day 28. There were no significant adverse effects noted in the supplementation group. Patients who reached a serum 25(OH)D level of >30 ng/mL on day 7 had a significantly lower 30-day mortality rate than did those who did not (5.9% vs 37.5%, p < 0.05). CONCLUSIONS: In our study, less than half of the patients reached adequate vitamin D levels after the enteral administration of high-dose vitamin D. A reduction in 30-day mortality was noted in the patients who achieved adequate vitamin D levels. TRIAL REGISTRATION CLINICALTRIALS. GOV ID: NCT04292873, Registered, March 1, 2020.

Score-based prediction model for severe vitamin D deficiency in patients with critical illness: development and validation.

BACKGROUND: Severe vitamin D deficiency (SVDD) dramatically increases the risks of mortality, infections, and many other diseases. Studies have reported higher prevalence of vitamin D deficiency in patients with critical illness than general population. This multicenter retrospective cohort study develops and validates a score-based model for predicting SVDD in patients with critical illness. METHODS: A total of 662 patients with critical illness were enrolled between October 2017 and July 2020. SVDD was defined as a serum 25(OH)D level of < 12 ng/mL (or 30 nmol/L). The data were divided into a derivation cohort and a validation cohort on the basis of date of enrollment. Multivariable logistic regression (MLR) was performed on the derivation cohort to generate a predictive model for SVDD. Additionally, a score-based calculator (the SVDD score) was designed on the basis of the MLR model. The model's performance and calibration were tested using the validation cohort. RESULTS: The prevalence of SVDD was 16.3% and 21.7% in the derivation and validation cohorts, respectively. The MLR model consisted of eight predictors that were then included in the SVDD score. The SVDD score had an area under the receiver operating characteristic curve of 0.848 [95% confidence interval (CI) 0.781-0.914] and an area under the precision recall curve of 0.619 (95% CI 0.577-0.669) in the validation cohort. CONCLUSIONS: This study developed a simple score-based model for predicting SVDD in patients with critical illness. TRIAL REGISTRATION: ClinicalTrials.gov protocol registration ID: NCT03639584. Date of registration: May 12, 2022.

Comparison of dexmedetomidine versus propofol sedation on microcirculation and organ injuries in critically ill surgical patients: A randomized controlled pilot study.

BACKGROUND: Recent studies have shown that dexmedetomidine may improve microcirculation and prevent organ failure. However, most evidence was obtained from experimental animals and patients receiving cardiac surgery with cardiopulmonary bypass. This study aimed to investigate the effect of dexmedetomidine on microcirculation and organ injuries in critically ill general surgical patients. METHODS: In this prospective randomized trial, patients admitted to the surgical intensive care unit after general surgery were enrolled and randomly allocated to the dexmedetomidine or propofol groups. Patients received continuous dexmedetomidine or propofol infusions to meet their requirement of sedation according to their grouping. At each time point, sublingual microcirculation images were obtained using the incident dark field video microscope. RESULTS: Overall, 60 patients finished the trial and were analyzed. Microcirculation parameters did not differ significantly between two groups. Heart rate at 4 h after ICU admission and mean arterial pressures at 12 h and 24 h after ICU admission were lower in the dexmedetomidine group than in the propofol group. At 24 h, serum aspartate aminotransferase (41 (25-118) vs 86 (34-129) U/L, p = 0.035) and alanine aminotransferase (50 (26-160) vs 68 (35-172) U/L, p = 0.019) levels were significantly lower in the dexmedetomidine group than in the propofol group. CONCLUSION: Microcirculation parameters did not differ significantly between the dexmedetomidine and propofol groups. At 24 h after ICU admission, serum liver enzyme levels were lower in patients receiving dexmedetomidine as compared to propofol.

Hypotension prediction index for prevention of intraoperative hypotension in patients undergoing general anesthesia: a randomized controlled trial.

BACKGROUND: Intraoperative hypotension is a common side effect of general anesthesia. Here we examined whether the Hypotension Prediction Index (HPI), a novel warning system, reduces the severity and duration of intraoperative hypotension during general anesthesia. METHODS: This randomized controlled trial was conducted in a tertiary referral hospital. We enrolled patients undergoing general anesthesia with invasive arterial monitoring. Patients were randomized 1:1 either to receive hemodynamic management with HPI guidance (intervention) or standard of care (control) treatment. Intraoperative hypotension treatment was initiated at HPI > 85 (intervention) or mean arterial pressure (MAP) < 65 mmHg (control). The primary outcome was hypotension severity, defined as a time-weighted average (TWA) MAP < 65 mmHg. Secondary outcomes were TWA MAP < 60 and < 55 mmHg. RESULTS: Of the 60 patients who completed the study, 30 were in the intervention group and 30 in the control group. The patients' median age was 62 years, and 48 of them were male. The median duration of surgery was 490 min. The median MAP before surgery presented no significant difference between the two groups. The intervention group showed significantly lower median TWA MAP < 65 mmHg than the control group (0.02 [0.003, 0.08] vs. 0.37 [0.20, 0.58], P < 0.001). Findings were similar for TWA MAP < 60 mmHg and < 55 mmHg. The median MAP during surgery was significantly higher in the intervention group than that in the control group (87.54 mmHg vs. 77.92 mmHg, P < 0.001). CONCLUSIONS: HPI guidance appears to be effective in preventing intraoperative hypotension during general anesthesia. Further investigation is needed to assess the impact of HPI on patient outcomes. TRIAL REGISTRATION: ClinicalTrials.gov (NCT04966364); 202105065RINA; Date of registration: July 19, 2021; The recruitment date of the first patient: July 22, 2021.

An observational study of microcirculation among healthy individuals by age and sex.

OBJECTIVE: This study measured normal ranges of microcirculatory parameters in healthy individuals and investigated differences in parameters by age and sex. METHODS: Participants were enrolled into three groups with equal numbers of male and female: young (20-39 years), middle-aged (40-59 years), and elderly (60-79 years). Sublingual microcirculation images were obtained using the incident dark field (IDF). RESULTS: A total of 75 female and 75 male healthy individuals were enrolled. The elderly group had a higher TVD (26.5 [2] vs. 25.2 [1.8]; p = 0.019) and a lower PPV (97 [2] vs. 98 [3]; p = 0.03) than did the young group. In the elderly group, systolic blood pressure (SBP) and mean arterial pressure (MAP) were moderately and positively correlated with MFI score (r = 0.407, p <  0.05, and r = 0.403, p <  0.05, respectively). The female participants had a lower MFI score than did the male participants (2.9 [2.8-3] vs. 3.0 [2.9-3]; p = 0.015). CONCLUSIONS: This study revealed the range of microcirculatory parameters between different ages and sexes in healthy individuals. We found that blood pressure levels were correlated with microcirculatory parameters, especially in elders and female.

Early prediction of delirium upon intensive care unit admission: Model development, validation, and deployment.

STUDY OBJECTIVE: To develop, validate, and deploy models for predicting delirium in critically ill adult patients as early as upon intensive care unit (ICU) admission. DESIGN: Retrospective cohort study. SETTING: Single university teaching hospital in Taipei, Taiwan. PATIENTS: 6238 critically ill patients from August 2020 to August 2021. MEASUREMENTS: Data were extracted, pre-processed, and split into training and testing datasets based on the time period. Eligible variables included demographic characteristics, Glasgow Coma Scale, vital signs parameters, treatments, and laboratory data. The predicted outcome was delirium, defined as any positive result (a score ≥ 4) of the Intensive Care Delirium Screening Checklist that was assessed by primary care nurses in each 8-h shift within 48 h after ICU admission. We trained models to predict delirium upon ICU admission (ADM) and at 24 h (24H) after ICU admission by using logistic regression (LR), gradient boosted trees (GBT), and deep learning (DL) algorithms and compared the models' performance. MAIN RESULTS: Eight features were extracted from the eligible features to train the ADM models, including age, body mass index, medical history of dementia, postoperative intensive monitoring, elective surgery, pre-ICU hospital stays, and GCS score and initial respiratory rate upon ICU admission. In the ADM testing dataset, the incidence of ICU delirium occurred within 24 h and 48 h was 32.9% and 36.2%, respectively. The area under the receiver operating characteristic curve (AUROC) (0.858, 95% CI 0.835-0.879) and area under the precision-recall curve (AUPRC) (0.814, 95% CI 0.780-0.844) for the ADM GBT model were the highest. The Brier scores of the ADM LR, GBT, and DL models were 0.149, 0.140, and 0.145, respectively. The AUROC (0.931, 95% CI 0.911-0.949) was the highest for the 24H DL model and the AUPRC (0.842, 95% CI 0.792-0.886) was the highest for the 24H LR model. CONCLUSION: Our early prediction models based on data obtained upon ICU admission could achieve good performance in predicting delirium occurred within 48 h after ICU admission. Our 24-h models can improve delirium prediction for patients discharged >1 day after ICU admission.

Successful management of delirium with dexmedetomidine in a patient with haloperidol-induced neuroleptic malignant syndrome: A case report.

BACKGROUND: We report a case of lorazepam-induced agitated delirium treated with haloperidol, which in turn triggered the onset of neuroleptic malignant syndrome (NMS). The latter condition, a medical emergency, was effectively treated with medical treatment and dexmedetomidine, a versatile and highly selective short-acting alpha-2 adrenergic agonist with sedative-hypnotic and anxiolytic effects. CASE SUMMARY: A 65-year-old man with a history of bipolar disorder presented to the emergency department with severe abdominal discomfort after binge eating. During his hospital stay, he received intravenous lorazepam for insomnia. On the next day, he became delirious and was thus treated with seven doses (5 mg each) of haloperidol over a 48 h period. Signs of NMS (hyperthermia, rigidity, myoclonus of upper limbs, impaired consciousness, tachypnea, and dark urine) became apparent and haloperidol was immediately suspended and brisk diuresis was initiated. On intensive care unit admission, he was confused, disoriented, and markedly agitated. Dexmedetomidine infusion was started with the goal of achieving a Richmond Agitation-Sedation Scale score of -1 or 0. NMS was resolved gradually and the patient stabilized, permitting discontinuation of dexmedetomidine after 3 d. CONCLUSION: Dexmedetomidine may be clinically helpful for the management of NMS, most likely because of its sympatholytic activity.

Early prediction of survival at different time intervals in sepsis patients: A visualized prediction model with nomogram and observation study.

OBJECTIVES: Sepsis is a major cause of death around the world. Complicated scoring systems require time to have data to predict short-term survival. Intensivists need a tool to predict survival in sepsis patients easily and quickly. MATERIALS AND METHODS: This retrospective study reviewed the medical records of adult patients admitted to the surgical intensive care units between January 2009 and December 2011 in National Taiwan University Hospital. For this study, 739 patients were enrolled. We recorded the demographic and clinical variables of patients diagnosed with sepsis. A Cox proportional hazard model was used to analyze the survival data and determine significant risk factors to develop a prediction model. This model was used to create a nomogram for predicting the survival rate of sepsis patients up to 3 months. RESULTS: The observed 28-day, 60-day, and 90-day survival rates were 71.43%, 52.53%, and 46.88%, respectively. The principal risk factors for survival prediction included age; history of dementia; Glasgow Coma Scale score; and lactate, creatinine, and platelet levels. Our model showed more favorable prediction than did Acute Physiology and Chronic Health Evaluation II and Sequential Organ Failure Assessment at sepsis onset (concordance index: 0.65 vs. 0.54 and 0.59). This model was used to create the nomogram for predicting the mortality at the onset of sepsis. CONCLUSION: We suggest that developing a nomogram with several principal risk factors can provide a quick and easy tool to early predict the survival rate at different intervals in sepsis patients.

Effects of perioperative dexmedetomidine infusion on renal function and microcirculation in kidney transplant recipients: a randomised controlled trial.

OBJECTIVE: Ischemia-reperfusion injury affects postoperative transplanted kidney function in kidney transplant recipients. Dexmedetomidine was reported to attenuate ischemia-reperfusion injury and improve microcirculation, but its propensity to cause bradycardia and hypotension may adversely affect microcirculation. This study investigated the effect of dexmedetomidine on postoperative renal function and sublingual microcirculation in kidney recipients. METHODS: The enrolled kidney transplant recipients were randomly allocated to the control group or dexmedetomidine group. After anaesthesia induction, patients in the dexmedetomidine group received dexmedetomidine infusion until 2 h after surgery. Sublingual microcirculation was recorded using an incident dark-field video microscope and analysed. The primary outcomes were the creatinine level on a postoperative day 2 and total vessel density at 2 h after surgery. RESULTS: A total of 60 kidney recipients were analysed, and the creatinine levels on postoperative day 2 were significantly lower in the dexmedetomidine group than in the control group (1.5 (1.1-2.4) vs. 2.2 (1.7-3.0) mg/dL, median difference -0.6 (95% CI, -0.7 to -0.5) mg/dL, p = .018). On a postoperative day 7, the creatinine levels did not differ significantly between the two groups. Total vessel density at 2 h after surgery did not differ significantly between the two groups. CONCLUSION: We found that early postoperative renal function was better in kidney transplant recipients receiving dexmedetomidine infusion, but total vessel density was not significantly different between the intervention and control groups. Key messagesIschemia-reperfusion injury affects postoperative transplanted kidney function, and dexmedetomidine was reported to attenuate ischemia-reperfusion injury and improve microcirculation in other clinical conditions.This study showed that early postoperative renal function was better in kidney transplant recipients receiving dexmedetomidine.Dexmedetomidine's side effect of bradycardia and hypotension may affect microcirculation, our results revealed that the perioperative sublingual microcirculation did not differ significantly in kidney transplant recipients receiving dexmedetomidine.

Unexpected cardio-circulatory arrest during a brain-dead donor organ retrieval.

According to the Maastricht classification category of donation after circulatory death (DCD), type IV DCD refers to brain-dead donors who are re-categorized after unexpected circulatory arrest before donor organ retrieval. Clinical management is challenging, even in intensive care units, where most of this type of organ donation occurs. We report a case of the first successful lung transplantation (LTx) using type IV DCD organ in Taiwan. The recipient's recovery was satisfactory, without acute or chronic organ dysfunction. When unexpected events made the brain-dead donors suffer from sudden onset of cardiac arrest before or during organ donation surgery, immediately switching the retrieval protocol from donation after brain death (DBD) to DCD could expand the donor pool and increase organ supply. The well-prepared and experienced transplant team and prompt protocol switch made this transplant surgery possible.

Prevalence of Vitamin D Deficiency and Associated Factors in Critically Ill Patients: A Multicenter Observational Study.

Background: Vitamin D deficiency is common in the general population worldwide, and the prevalence and severity of vitamin D deficiency increase in critically ill patients. The prevalence of vitamin D deficiency in a community-based cohort in Northern Taiwan was 22.4%. This multicenter cohort study investigated the prevalence of vitamin D deficiency and associated factors in critically ill patients in Northern Taiwan. Methods: Critically ill patients were enrolled and divided into five groups according to their length of stay at intensive care units (ICUs) during enrolment as follows: group 1, <2 days with expected short ICU stay; group 2, <2 days with expected long ICU stay; group 3, 3-7 days; group 4, 8-14 days; and group 5, 15-28 days. Vitamin D deficiency was defined as a serum 25-hydroxyvitamin D (25(OH)D) level < 20 ng/ml, and severe vitamin D deficiency was defined as a 25(OH)D level < 12 ng/ml. The primary analysis was the prevalence of vitamin D deficiency. The exploratory analyses were serial follow-up vitamin D levels in group 2, associated factors for vitamin D deficiency, and the effect of vitamin D deficiency on clinical outcomes in critically ill patients. Results: The prevalence of vitamin D deficiency was 59% [95% confidence interval (CI) 55-62%], and the prevalence of severe vitamin D deficiency was 18% (95% CI 15-21%). The median vitamin D level for all enrolled critically ill patients was 18.3 (13.7-23.9) ng/ml. In group 2, the median vitamin D levels were <20 ng/ml during the serial follow-up. According to the multivariable analysis, young age, female gender, low albumin level, high parathyroid hormone (PTH) level, and high sequential organ failure assessment (SOFA) score were significantly associated risk factors for vitamin D deficiency. Patients with vitamin D deficiency had longer ventilator use duration and length of ICU stay. However, the 28- and 90-day mortality rate were not associated with vitamin D deficiency. Conclusions: This study demonstrated that the prevalence of vitamin D deficiency is high in critically ill patients. Age, gender, albumin level, PTH level, and SOFA score were significantly associated with vitamin D deficiency in these patients.

Prevalence, risk factors, and optimized management of moderate-to-severe thirst in the post-anesthesia care unit.

Post-operative thirst is common and may cause intense patient discomfort. The aims of this retrospective study conducted in a high-volume post-anesthesia care unit (PACU) were as follows: (1) to examine the prevalence of moderate-to-severe post-operative thirst-defined as a numerical rating scale (NRS) score of 4 or higher, (2) to identify the main risk factors for moderate-to-severe post-operative thirst, and (3) to maximize the efficacy and safety of thirst management through a quality improvement program. During a 1-month quality improvement program conducted in August 2018, a total of 1211 adult patients admitted to our PACU were examined. Moderate-to-severe thirst was identified in 675 cases (55.8%). The use of glycopyrrolate during anesthesia was associated with moderate-to-severe thirst (71.7% versus 66.4%, respectively, p = 0.047; adjusted odds ratio: 1.46, p = 0.013). Following a safety assessment, ice cubes, room temperature water, or an oral moisturizer were offered to patients. A generalized estimating equation model revealed that ice cubes were the most effective means for thirst management-resulting in an estimated thirst intensity reduction of 0.93 NRS points at each 15-min interval assessment (p < 0.001)-followed by room temperature water (- 0.92/time-point, p < 0.001) and the oral moisturizer (- 0.60/time-point; p < 0.001). Patient satisfaction (rated from 1 [definitely dissatisfied] to 5 [very satisfied]) followed a similar pattern (ice cubes: 4.22 ± 0.58; room temperature water: 4.08 ± 0.55; oral moisturizer: 3.90 ± 0.55, p < 0.001). The use of glycopyrrolate-an anticholinergic agent that reduces salivary secretion-was the main independent risk factor for moderate-to-severe post-operative thirst. Our findings may provide clues towards an optimized management of thirst in the immediate post-operative period.

Mini-fluid challenge test predicts stroke volume and arterial pressure fluid responsiveness during spine surgery in prone position: A STARD-compliant diagnostic accuracy study.

The study was designed to verify if mini-fluid challenge test is more reliable than dynamic fluid variables in predicting stroke volume (SV) and arterial pressure fluid responsiveness during spine surgery in prone position with low-tidal-volume ventilation.Fifty patients undergoing spine surgery in prone position were included. Fluid challenge with 500 mL of colloid over 15 minutes was given. Changes in SV and systolic blood pressure (SBP) after initial 100 mL were compared with SV, pulse pressure variation (PPV), SV variation (SVV), plethysmographic variability index (PVI), and dynamic arterial elastance (Eadyn) in predicting SV or arterial pressure fluid responsiveness (15% increase or greater).An increase in SV of 5% or more after 100 mL predicted SV fluid responsiveness with area under the receiver operating curve (AUROC) of 0.90 (95% confidence interval [CI], 0.82 to 0.99), which was significantly higher than that of PPV (0.71 [95% CI, 0.57 to 0.86]; P = .01), and SVV (0.72 [95% CI, 0.57 to 0.87]; P = .03). A more than 4% increase in SBP after 100 mL predicted arterial pressure fluid responsiveness with AUROC of 0.86 (95% CI, 0.71-1.00), which was significantly higher than that of Eadyn (0.52 [95% CI, 0.33 to 0.71]; P = .01).Changes in SV and SBP after 100 mL of colloid predicted SV and arterial pressure fluid responsiveness, respectively, during spine surgery in prone position with low-tidal-volume ventilation.

Effects of endotoxin adsorber hemoperfusion on sublingual microcirculation in patients with septic shock: a randomized controlled trial.

BACKGROUND: Endotoxins can induce an excessive inflammatory response and result in microcirculatory dysfunction. Polymyxin-B hemoperfusion (PMX-HP) has been recognized to effectively remove endotoxins in patients with sepsis and septic shock, and a rat sepsis model revealed that PMX-HP treatment can maintain a better microcirculation. The primary aim of this study was to investigate the effect of PMX-HP on microcirculation in patients with septic shock. METHODS: Patients with septic shock were enrolled and randomized to control and PMX-HP groups. In the PMX-HP group, patients received the first session of PMX-HP in addition to conventional septic shock management within 24 h after the onset of septic shock; the second session of PMX-HP was provided after another 24 h as needed. RESULTS: Overall, 28 patients finished the trial and were analyzed. The mean arterial pressure and norepinephrine infusion dose did not differ significantly between the control and PMX-HP groups after PMX-HP treatment. At 48 h after enrollment, total vessel density (TVD) and perfused vessel density (PVD) were higher in the PMX-HP group than in the control group [TVD 24.2 (22.1-24.9) vs. 21.1 (19.9-22.9) mm/mm2; p = 0.007; PVD 22.9 (20.9-24.9) vs. 20.0 (18.9-21.6) mm/mm2, p = 0.008]. CONCLUSIONS: This preliminary study observed that PMX-HP treatment improved microcirculation but not clinical outcomes in patients with septic shock at a low risk of mortality. Nevertheless, larger multicenter trials are needed to confirm the effect of PMX-HP treatment on microcirculation in patients with septic shock at intermediate- and high-risk of mortality. Trial registration ClinicalTrials.gov protocol registration ID: NCT01756755. Date of registration: December 27, 2012. First enrollment: October 6, 2013. https://clinicaltrials.gov/ct2/show/NCT01756755.