Implementing pain, agitation, delirium, and sleep deprivation protocol in critically ill patients: A pilot study on pharmacological interventions.

Critically ill patients frequently experience pain, agitation, delirium, and sleep deprivation, which have been linked to increased mortality and unfavorable clinical outcomes. To address these challenges, the Pain, Agitation, Delirium, and Sleep Deprivation (PADS) protocol was developed, aiming to mitigate mortality and improve clinical outcomes. This study focuses on assessing the protocol's impact using a robust before-and-after study design in the medical and surgical intensive care units (ICUs) at Ramathibodi Hospital. Using an observational approach, this study compares clinical outcomes before and after implementing the PADS protocol in the ICUs. Two patient cohorts were identified: the "before" group, comprising 254 patients with retrospective data collected between May 2018 and September 2019, and the "after" group, consisting of 255 patients for whom prospective data was collected from May to September 2020. Analysis reveals improvements in the after group. Specifically, there was a significant increase in 14-day ICU-free days (9.95 days vs. 10.40 days, p value = 0.014), a decrease in delirium incidence (18.1% vs. 16.1%, p value < 0.001), and a significant reduction in benzodiazepine usage (38.6% vs. 24.6%, p value = 0.001) within the after group. This study emphasizes the protocol's potential to improve patient care and highlights its significance in the ICU context.

Pharmacokinetics and pharmacodynamics studies of a loading dose of cisatracurium in critically ill patients with respiratory failure.

BACKGROUND: Previous studies reported a slow neuromuscular response with the currently recommended dose of cisatracurium in critically ill patients. Pharmacokinetic and pharmacodynamic studies of cisatracurium in critically ill patients are still limited. To our knowledge, this is the first study performed to better understand the pharmacokinetics (PKs) and pharmacodynamics (PDs) of a loading dose of cisatracurium and to identify factors that affect PK and PD changes in critically ill patients. METHODS: A prospective PKs and PDs study was designed. Arterial blood samples of 10 critically ill patients with respiratory failure were collected after administering a loading dose of 0.2 mg/kg of cisatracurium. Plasma cisatracurium and laudanosine concentrations were determined using liquid chromatography-tandem mass spectrometry. The achievement of the desired pharmacodynamic response was evaluated by both 1) clinical assessment and 2) train-of-four monitoring. The PK/PD indices were analyzed for their correlation with patient'characteristics and other factors. RESULTS: The one-compartment model best described the plasma pharmacokinetic parameters of cisatracurium. The volume of distribution at steady state and total clearance were 0.11 ± 0.04 L/kg and 2.74 ± 0.87 ml/minute/kg, respectively. The mean time to train-of-four 0/4 was 6 ± 3.86 minutes. A time to the desired pharmacodynamic response of less than 5 minutes was found in 10% of the patients. A positive correlation was found between cisatracurium concentration and albumin levels and between pharmacokinetics data and patient factors [partial pressure of carbon dioxide and respiratory alkalosis]. CONCLUSION: The currently recommended loading dose of cisatracurium might not lead to the desired pharmacodynamic response in critically ill patients with respiratory failure. TRIAL REGISTRATION: ClinicalTrials.gov , NCT03337373. Registered on 9 November 2017.

Incidence and clinical manifestation of iatrogenic opioid withdrawal syndrome in mechanically ventilated patients.

OBJECTIVE: The incidence of iatrogenic opioid withdrawal syndrome (IOWS) in mechanically ventilated adults has been questioned in settings driven by analgosedation strategies. This study aimed to describe the incidence, risk factors and clinical impact of IOWS in mechanically ventilated adults. METHODS: This prospective, observational study was performed between 1 January and 31 August 2018. IOWS was identified based on the presence of at least three signs or symptoms according to the Diagnostic and Statistical Manual 5th edition (DSM-5) criteria after opioid discontinuation or rate reduction. Incidence of IOWS, patient characteristics, opioid administration, and the impact of IOWS on the duration of mechanical ventilator and length of stay in the intensive care unit (ICU) were collected. RESULTS: Thirteen out of 55 patients (23.6%) manifested withdrawal symptoms. Two patients in the non-withdrawal group also developed hypertensive urgency after opioid discontinuation. Patients who received rapid once-daily weaning, especially rate reduction more than 50 µg as fentanyl equivalent per hour, were associated with IOWS. However, there was no statistically significant difference in ventilator-free days and ICU-free days. CONCLUSIONS: These findings showed that approximately one-fourth of mechanically ventilated patients who received opioid infusion experienced IOWS. Monitoring for IOWS is recommended especially in patients who received rapid weaning rate of opioids. Future studies to develop IOWS assessment tools with the change of hemodynamic parameters should be performed. TRIAL REGISTRATION: This trial was registered in ClinicalTrials.gov: identifier NCT03374722, date of registration 15 December 2018.

Effects of thiamine on vasopressor requirements in patients with septic shock: a prospective randomized controlled trial.

BACKGROUND: Thiamine, an essential vitamin for aerobic metabolism and glutathione cycling, may decrease the effects of critical illnesses. The objective of this study was to determine whether intravenous thiamine administration can reduce vasopressor requirements in patients with septic shock. METHODS: This study was a prospective randomized double-blind placebo-controlled trial. We included adult patients with septic shock who required a vasopressor within 1-24 h after admission between March 2018 and January 2019 at a tertiary hospital in Thailand. Patients were divided into two groups: those who received 200 mg thiamine or those receiving a placebo every 12 h for 7 days or until hospital discharge. The primary outcome was the number of vasopressor-free days over 7 days. The pre-defined sample size was 31 patients per group, and the study was terminated early due to difficult recruitment. RESULTS: Sixty-two patients were screened and 50 patients were finally enrolled in the study, 25 in each group. There was no difference in the primary outcome of vasopressor-free days within the 7-day period between the thiamine and placebo groups (mean: 4.9 days (1.9) vs. 4.0 days (2.7), p = 0.197, mean difference - 0.9, 95% CI (- 2.9 to 0.5)). However, the reductions in lactate (p = 0.024) and in the vasopressor dependency index (p = 0.02) at 24 h were greater among subjects who received thiamine repletion vs. the placebo. No statistically significant difference was observed in SOFA scores within 7 days, vasopressor dependency index within 4 days and 7 days, or 28-day mortality. CONCLUSIONS: Thiamine was not associated to a significant reduction in vasopressor-free days over 7-days in comparison to placebo in patients with septic shock. Administration of thiamine could be associated with a reduction in vasopressor dependency index and lactate level within 24 h. The study is limited by early stopping and low sample size. TRIAL REGISTRATION: TCTR, TCTR20180310001. Registered 8 March 2018, http://www.clinicaltrials.in.th/index.php?tp=regtrials&menu=trialsearch&smenu=fulltext&task=search&task2=view1&id=3330 .

Clinical outcomes of empirical high-dose meropenem in critically ill patients with sepsis and septic shock: a randomized controlled trial.

BACKGROUND: Appropriate antimicrobial dosing is challenging because of changes in pharmacokinetics (PK) parameters and an increase in multidrug-resistant (MDR) organisms in critically ill patients. This study aimed to evaluate the effects of an empirical therapy of high-dose versus standard-dose meropenem in sepsis and septic shock patients. METHODS: We performed a prospective randomized open-label study to compare the changes of modified sequential organ failure assessment (mSOFA) score and other clinical outcomes of the high-dose meropenem (2-g infusion over 3 h every 8 h) versus the standard-dose meropenem (1-g infusion over 3 h every 8 h) in sepsis and septic shock patients. Patients' characteristics, clinical and microbiological outcomes, 14 and 28-day mortality, vasopressor- and ventilator-free days, intensive care unit (ICU) and hospital-free days, percent of the time of antibiotic concentrations above the minimum inhibitory concentration (%T>MIC), and safety were assessed. RESULTS: Seventy-eight patients were enrolled. Median delta mSOFA was comparable between two groups (- 1 in the high-dose group vs. - 1 in the standard-dose group; P value = 0.75). There was no difference between the two groups regarding clinical and microbiological cure, 14- and 28-day mortality, vasopressor- and ventilator-free days, and ICU- and hospital-free days. In patients admitted from the emergency department (ED) with a mSOFA score ≥ 7, the high-dose group demonstrated significantly better microbiological cure compared with the standard-dose group (75% (9/12 patients) vs. 20% (2/10 patients); P value = 0.03). Likewise, the high-dose group presented higher microbiological cure rate in patients admitted from ED who had either APACHE II score > 20 (83.3% (10/12) vs. 28.6% (2/7); P value = 0.045) or on mechanical ventilator (87.5% (7/8) vs. 23.1% (3/13); P value = 0.008) than the standard-dose group. Adverse events were comparable between the two groups. CONCLUSIONS: Empirical therapy with the high-dose meropenem presented comparable clinical outcomes to the standard-dose meropenem in sepsis and septic shock patients. Besides, subgroup analysis manifested superior microbiological cure rate in sepsis or septic shock patients admitted from ED. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03344627, registered on November 17, 2017.

Pharmacokinetics and Penetration of Sitafloxacin into Alveolar Epithelial Lining Fluid in Critically Ill Thai Patients with Pneumonia.

Sitafloxacin showed potent activity against various respiratory pathogens. Blood and bronchoalveolar lavage (BAL) fluid samples were obtained from 12 subjects after a single oral dose of sitafloxacin 200 mg. The mean ± SD (median) maximum ratio of epithelial lining fluid (ELF) to unbound plasma concentration was 1.02 ± 0.58 (1.33). The penetration ratios based on the mean and median area under the curve from 0 to 8 h (AUC0-8) were 0.85 and 0.79 µg · h/ml, respectively. Sitafloxacin penetrates well into ELF in critically ill Thai patients with pneumonia. (This study has been registered in the Thai Clinical Trials Registry [TCTR] under registration no. TCTR20170222001.).

The Correlation Between Arterial Lactate and Venous Lactate in Patients With Sepsis and Septic Shock.

BACKGROUND: Applying peripheral venous lactate instead of arterial lactate in clinical practice is questionable because of deviation between both values. We aimed to find the relationship between the arterial lactate and the peripheral venous lactate before reasoned that the venous lactate could be used in substitution to the arterial lactate in sepsis. METHODS: We conducted a prospective, cross-sectional study at a university hospital. The patients with sepsis in ICU who required lactate level monitoring were enrolled in this research. The correlation and agreement between arterial lactate (A-LACT) and peripheral venous lactate (V-LACT) were the primary outcomes. RESULTS: A total of 63 paired samples were collected. The A-LACT and V-LACT were strongly correlated ( r = .934, P < .0001, r2 = .873). The regression equation was A-LACT = (0.934 × V-LACT) - 0.236. The mean difference between V-LACT and A-LACT was 0.66 ± 1.53 mmol/L. The 95% limits of agreement were between -3.66 and 2.33 mmol/L. The V-LACT ≥ 4 mmol/L can predict A-LACT level ≥ 4 mmol/L with 87.5% sensitivity and 91.5% specificity, and the area under receiver operating characteristic curve was 0.948. CONCLUSION: The present study demonstrated a strong correlation between A-LACT and V-LACT, but an agreement between both parameters was poor. We suggest not to use the V-LACT in substitution to the A-LACT in sepsis regarding the absolute value and clearance rate, but the V-LACT ≥ 4.5 mmol/L may be used for predicting the A-LACT ≥ 4 mmol/L.

Impact of pharmaceutical care on pain and agitation in a medical intensive care unit in Thailand.

Background Currently, a lack of pharmaceutical care exists concerning pain and agitation in medical intensive care units (MICU) in Thailand. Pharmaceutical care focusing on analgesics/sedatives would improve clinical outcomes. Objective To investigate the impact of pharmaceutical care of pain and agitation on ICU length of stay (LOS), hospital LOS, ventilator days and mortality. Setting The MICU of a university hospital. Method A before/after study was conducted on mechanically ventilated patients receiving analgesics/sedatives. Medical chart reviews and data collection were conducted in the retrospective group (no pharmacists involved). In the prospective group, pharmacists involved with the critical care team helped select analgesics/sedatives for individual patients. Main outcome measure ICU LOS Results In total, 90 and 66 patients were enrolled in retrospective and prospective groups, respectively. The median duration of ICU LOS was reduced from 10.00 (2.00-72.00) in the retrospective group to 6.50 days (2.00-30.00) in the prospective group (p = 0.002). The median hospital stay was reduced from 30.50 days (2.00-119.00) in the retrospective group to 17.50 days (2.00-110.00) in the prospective group (p < 0.001). Also, the median ventilator days was reduced from 14.00 days (2.00-90.00) to 8.50 days (1.00-45.00), p = 0.008. Mortality was 53.03% in the prospective group and 46.67% in the retrospective group (p = 0.432). Conclusion Pharmacist participation in a critical care team resulted in a significant reduction in the duration of ICU LOS, hospital LOS and ventilator days, but not mortality.

Anticoagulation for renal replacement therapy for patients with acute kidney injury.

Patients with acute kidney injury are generally prothrombotic, and as such prone to increased risk of clotting in extracorporeal renal replacement therapy (RRT) circuits. Although some patients may be adequately treated by intermittent RRT, however due to cardiovascular instability many patients are treated by continuous renal replacement therapy (CCRT) or prolonged intermittent renal replacement therapy (PIRRT). Clotting in the RRT circuit not only reduces the efficiency of solute clearances, affects fluid balance, but also has economic health care costs. The longer duration RRT modes, CRRT and PIRRT are more prone to clotting, and more dependent on adequate anticoagulation. This review will compare the currently available systemic and regional anticoagulation options for CRRT and PIRRT for the patient with acute kidney injury.

Experience of percutaneous dilatational tracheostomy by using Grigg's technique in Siriraj Hospital.

BACKGROUND: Percutaneous dilatational tracheostomy (PDT) was increasingly performed after the commercial kit was available in 1985. Several studies showed that PDT was equivalent to surgical tracheostomy considering perioperative and long-term complications and PDT was more cost-effective and provide greater feasibility in terms of bedside capacity and nonsurgical operation. MATERIAL AND METHOD: The data of patients who were performed PDT at Division of Respiratory Disease and Tuberculosis, Department of Medicine, Faculty of Medicine Siriraj Hospital were retrospectively reviewed since March 2007 to December 2011. All procedures were done at bedside in intensive care unit or general ward of internal medicine under intravenous anesthesia. PDT was performed by using Griggs' technique. This technique is based on Seldinger guidewire technique and uses the guidewire dilator forceps (GWDFs) to enlarge the hole in the trachea under flexible bronchoscopic visualization. RESULTS: Ninety-one patients were enrolled with a mean age of 68 years old (range 17-100). Majority of patients had American Society of Anesthesiologist (ASA) classification 3. The most common indication for tracheostomy was failure to wean from the mechanical ventilator (68 patients; 74.7%). Fifty-two procedures (57.1%) were done at intensive care unit and 39 procedures (42.9%) were done at general ward of internal medicine. Mean duration of procedure was 18 minutes (range 5-90). The rate of perioperative complication was 11.0%. Five patients (5.5%) had desaturation and all of them were improved by short disruption of the procedure for ventilatory support. Three patients (3.3%) had moderate bleeding and one (1.1 %) had excessive bleeding that were stopped by electrocauterization and pressure compression. There was 1 serious perioperative complication that was accidental extubation. No perioperative or postoperative mortality that related to procedure was found. CONCLUSION: PDT is a safe procedure and can be performed easily and rapidly at the bedside either in intensive care unit or general ward with closed monitoring. Proper patient selection and attention to technical detail are necessary in maintaining low complication rates.