Adjunctive ketamine for sedation in critically ill mechanically ventilated patients: an active-controlled, pilot, feasibility clinical trial.

OBJECTIVE: Ketamine has been shown to decrease sedative requirements in intensive care unit (ICU). Randomized trials are limited on patient-centered outcomes. We designed this pilot trial to evaluate the feasibility of a large randomized controlled trial (RCT) testing the effect of ketamine as an adjunct analgosedative compared with standard of care alone as a control group (CG) in critically ill patients with mechanical ventilation (MV). We also provided preliminary evidence on clinically relevant outcomes to plan a larger trial. MATERIAL AND METHODS: Pilot, active-controlled, open-label RCT was conducted at medical, surgical, and transplant ICUs at a large tertiary and quaternary care medical institution (King Faisal Specialist Hospital and Research Center, Saudi Arabia). The study included adult patients who were intubated within 24 h, expected to require MV for the next calendar day, and had institutional pain and sedation protocol initiated. Patients were randomized in a 1:1 ratio to adjunct ketamine infusion 1-2 µg/kg/min for 48 h or CG alone. RESULTS: Of 437 patients screened from September 2019 through November 2020, 83 (18.9%) patients were included (43 in CG and 40 in ketamine) and 352 (80.5%) were excluded. Average enrollment rate was 3-4 patients/month. Consent and protocol adherence rates were adequate (89.24% and 76%, respectively). Demographics were balanced between groups. Median MV duration was 7 (interquartile range [IQR] 3-9.25 days) in ketamine and 5 (IQR 2-8 days) in CG. Median VFDs was 19 (IQR 0-24.75 days) in ketamine and 19 (IQR 0-24 days) in the CG (p = 0.70). More patients attained goal Richmond Agitation-Sedation Scale at 24 and 48 h in ketamine (67.5% and 73.5%, respectively) compared with CG (52.4% and 66.7%, respectively). Sedatives and vasopressors cumulative use, and hemodynamic changes were similar. ICU length-of-stay was 12.5 (IQR 6-21.2 days) in ketamine, compared with 12 (IQR 5.5-23 days) in CG. No serious adverse events were observed in either group. CONCLUSIONS: Ketamine as an adjunct analgosedative agent appeared to be feasible and safe with no negative impact on outcomes, including hemodynamics. This pilot RCT identified areas of improvement in study protocol before conducting a large, adequately powered, multicenter RCT which is likely justified to investigate ketamine association with patient-centered outcomes further. Trial registration ClinicalTrials.gov: NCT04075006. Registered on 30 August 2019. Current controlled trials: ISRCTN14730035. Registered on 3 February 2020.

The Prevalence of Barrett's Esophagus Among a Saudi Arabian Population.

BACKGROUND: While gastroesophageal reflux disease (GERD) is common in Middle Eastern countries, little data exists on the epidemiology of Barrett's esophagus (BE). AIMS: We aimed to determine the prevalence of BE among patients undergoing esophagogastroduodenoscopy (EGD) in a cohort of Saudi patients. METHODS: We retrospectively reviewed the endoscopy database at an academic tertiary care center. Consecutive adult patients who underwent an EGD for any indication between May 2014 and December 2018 were included. The prevalence of both endoscopically and histologically reported BE was determined. Multivariate regression analysis was used to identify factors associated with BE. RESULTS: A total of 2805 patients were included. The mean age was 48 years (± 18.6) and 38.7% were male patients. BE was reported endoscopically in 18 (0.64%) and confirmed histologically in 9 patients (0.32%). Among patients with endoscopically reported BE, the mean age was 50.3 (± 16.1) years and 13 (72.2%) were male patients. Of patients with BE, short-segment BE was reported in 14 (77.8%) patients. Among the 9 patients with histologically confirmed BE; only one patient had dysplastic BE. On univariate analysis, BE was associated with male gender (p < 0.01), but not with age > 50, hiatal hernia, obesity or EGD performed for GERD related indications. On multivariate regression analysis, male gender was the only factor associated with BE (aOR 3.77, 95% CI 1.39-11.97, p = 0.01). CONCLUSION: BE was endoscopically reported in 0.64% and histologically confirmed in 0.32% of this cohort of Saudi patients. Male gender was the only factor associated with BE.

Adjunct low-dose ketamine infusion vs standard of care in mechanically ventilated critically ill patients at a Tertiary Saudi Hospital (ATTAINMENT Trial): study protocol for a randomized, prospective, pilot, feasibility trial.

BACKGROUND: A noticeable interest in ketamine infusion for sedation management has developed among critical care physicians for critically ill patients. The 2018 Pain, Agitation/sedation, Delirium, Immobility, and Sleep disruption guideline suggested low-dose ketamine infusion as an adjunct to opioid therapy to reduce opioid requirements in post-surgical patients in the intensive care unit (ICU). This was, however, rated as conditional due to the very low quality of evidence. Ketamine has favorable characteristics, making it an especially viable alternative for patients with respiratory and hemodynamic instability. The Analgo-sedative adjuncT keTAmine Infusion iN Mechanically vENTilated ICU patients (ATTAINMENT) trial aims to assess the effect and safety of adjunct low-dose continuous infusion of ketamine as an analgo-sedative compared to standard of care in critically ill patients on mechanical ventilation (MV) for ≥ 24 h. METHODS/DESIGN: This trial is a prospective, randomized, active controlled, open-label, pilot, feasibility study of adult ICU patients (> 14 years old) on MV. The study will take place in the adult ICUs in the King Faisal Specialist Hospital and Research Center (KFSH&RC), Riyadh, Saudi Arabia, and will enroll 80 patients. Patients will be randomized post-intubation into two groups: the intervention group will receive an adjunct low-dose continuous infusion of ketamine plus standard of care. Ketamine will be administered over a period of 48 h at a fixed infusion rate of 2 µg/kg/min (0.12 mg/kg/h) in the first 24 h followed by 1 µg/kg/min (0.06 mg/kg/h) in the second 24 h. The control group will receive standard of care in the ICU (propofol and/or fentanyl and/or midazolam) according to the KFSH&RC sedation and analgesia protocol as clinically appropriate. The primary outcome is MV duration until ICU discharge, death, extubation, or 28 days post-randomization, whichever comes first. DISCUSSION: The first patient was enrolled on 1 September 2019. As of 10 October 2019, a total of 16 patients had been enrolled. We expect to complete the recruitment by 31 December 2020. The findings of this pilot trial will likely justify further investigation for the role of adjunct low-dose ketamine infusion as an analgo-sedative agent in a larger, multicenter, randomized controlled trial. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04075006. Registered on 30 August 2019. Current controlled trials: ISRCTN14730035. Registered on 3 February 2020.

Increases in Heart Rate Variability Signal Improved Outcomes in Rapid Response Team Consultations: A Cohort Study.

BACKGROUND: Reduced heart rate variability (HRV) indicates dominance of the sympathetic system and a state of "physiologic stress." We postulated that, in patients with critical illness, increases in HRV might signal successful resuscitation and improved prognosis. METHODS: We carried out a prospective observational study of HRV on all patients referred to the rapid response team (RRT) and correlated with serial vital signs, lactate clearance, ICU admission, and mortality. RESULTS: Ninety-one patients were studied. Significantly higher HRV was observed in patients who achieved physiological stability and did not need ICU admission: ASDNN 19 versus 34.5, p=0.032; rMSSD 13.5 versus 25, p=0.046; mean VLF 9.4 versus 17, p=0.021; mean LF 5.8 versus 12.4, p=0.018; and mean HF 4.7 versus 10.5, p=0.017. ROC curves confirmed the change in very low frequencies at 2 hours as a strong predictor for ICU admission with an AUC of 0.772 (95% CI 0.633, 0.911, p=0.001) and a cutoff value of -0.65 associated with a sensitivity of 78.6% and a specificity of 61%. CONCLUSIONS: Reduced HRV, specifically VLF, appears closely related to greater severity of critical illness, identifies unsuccessful resuscitation, and can be used to identify consultations that need early ICU admission.

[MEDICATIONS DEPRESCRIBING IN ELDERLY NURSING HOME RESIDENTS].

INTRODUCTION: Polypharmacy, inappropriate prescribing and adverse drug reactions are frequent and important among elderly nursing home residents. Few clinical trials have evaluated systematic withdrawal of medications in nursing homes. OBJECTIVES: To compare the effect of a controlled deprescribing intervention against the usual care in elderly nursing home residents. METHODS: The present deprescribing intervention was conducted in two departments at the Shfaram Geriatric Center (Beet Alenaya). Two departments at the "Hemdat Avot" nursing home were the control arm. The intervention was a withdrawal or stepwise tapering of a target medication. The main outcome was the number of participants in whom medication withdrawal or tapering could be achieved. RESULTS: A total of 55 participants completed the intervention and follow-up. The results showed that 65.5 % of the intervention group had discontinued a medication use compared with 27% of the control group (risk difference, 73% [95%CI, 58%-85%]; intracluster correlation, 0.001; number needed to treat, 2.60). Dose reduction occurred in an additional 11%. In multivariate sub-analyses, age greater than 80 years, sex and concomitant polypharmacy (10 drugs or more per day) did not have a significant interaction effect with medication therapy discontinuation. CONCLUSION: A controlled deprescribing intervention in nursing homes was feasible and acceptable to participants. Such interventions should be further evaluated in larger randomized controlled trials.

Dimensional Changes in Alveolar Ridge Following Extraction of Teeth in the Maxillary Premolar Area in Subjects with Thick and Thin Gingival Biotypes: A Pilot Study.

This study investigated changes in residual ridge dimensions after tooth extraction among thin and thick gingival biotypes. Fifteen patients who required extraction of maxillary premolars were classified according to gingival biotypes (10 teeth in 9 participants were included in the thick group, and 6 teeth in 6 participants were included in the thin group). Minimally traumatic extractions were carried out using periotomes and rotational movement of teeth. At the time of extraction an osteometer was used to measure the thickness of the labial plate and the bony alveolar ridge at the extraction site by penetrating the tissues until bone was reached 5 mm, 7 mm, and 10 mm below the midpoint of the crest of the facial and palatal gingival margins. Standardized radiographs were taken immediately and after 3 months. The results of this study show minimal differences in dimensional changes following extraction of premolar teeth in thick and thin gingival biotypes. Significantly greater bone loss was detected in both gingival biotypes when the labial plate thickness was less than 1.5 mm, especially in alveolar ridge height.

The rapid response team in outpatient settings identifies patients who need immediate intensive care unit admission: A call for policy maker.

BACKGROUND: Caregivers in the ambulatory care setting with differing clinical background could encounter a patient at high risk of deterioration. In the absence of a dedicated acute care team, the response to an unanticipated medical emergencies in these settings is likely to have a poor outcome. OBJECTIVE: To describe our experience in implementing an intensivist-led rapid response team (RRT) in the outpatient settings that identified patients who needed immediate Intensive Care Unit (ICU) admission. The effect on in hospital arrests, mortality, and ICU outcome is not the scope of this study. MATERIALS AND METHODS: This retrospective descriptive study was performed from January 1, 2009 to December 31, 2011 in a tertiary hospital. Data from hospital records were used (none from patients' records). Consent was not needed. MEASUREMENTS: Direct ICU admissions from the outpatient areas. RESULTS: There were 90 patients cared for by RRT in the outpatient's settings, 76 adult, and 14 pediatric patients. A total of12 adult patients were transferred directly to ICU. Among the patient who were transferred to the emergency department, additional four patients required to be transferred to ICU (total 16 patients [17.7%], 15 adult, and one pediatric patient). Follow-up at 24 h in the ICU showed death of one adult oncology patient (6.25%), and discharge of two patients (12.5%). Nine patients (81%) were still sick to require longer ICU stay. CONCLUSION: Intensivist-led RRT in outpatient settings identifies patients who are critically ill and in need of immediate ICU admission. Thus, an intensivist-led RRT policy in the outpatient settings needs to be implemented hospital wide.

Making a Difference in Eye Care of the Critically Ill Patients.

Ocular surface disorders are frequently encountered in patients under sedation and paralyzed patients in intensive care units (ICUs). In the ICUs, treatment is usually focused on the management of organ failures, and eye care becomes a side issue. As a result, ophthalmological complications do occur (incidence ranges from 3.6% to 60%) and are frequently overlooked in this setting. To identify the best available evidence in providing the best eye care to prevent exposure keratopathy, a literature review was performed. The databases of PUBMED, COCHRAN, and EMBASE library were searched. We only looked at higher quality articles. Among various eye care measures that have been advocated to prevent exposure keratopathy, the most effective is the application of polyethylene covers. Early diagnosis and effective treatment will help prevent microbial keratitis and visual loss.

The summer premedical program for matriculating medical students: a student-led initiative.

The freshman academic year is one of the most difficult years that a medical student experiences in his/her academic life at a medical school. Freshmen are frequently faced with several challenges, such as adaptation to a new academic environment and its associated different methods of teaching, learning, skills, and assessment. The aim of this study was to describe a 4-wk innovative summer premedical program developed by senior medical students at the College of Medicine, Alfaisal University, in an attempt to improve/smooth the experience(s) of prospective freshmen. This report describes the objectives/strategies/methodologies used to tackle the top three identified freshman challenges, namely, 1) advancement of the academic/scholastic/educational background, 2) the development of college-required skills to succeed and excel in the freshman year, and 3) adaption to the college environment. At the end of the program, a survey was conducted to evaluate the effectiveness of the summer premedical program. Seventy-two students attended this program over the past three summers from 2010 to 2012, and twenty-nine students answered the survey with a response rate of 74.1%. Overall, >90% of the survey respondents reported an improvement in their understanding of basic medical science, integration, presentation skills, medical terminology, and junior-senior relationships. Furthermore, the survey highlighted the need for more focus on skills such as time management, participation in large-group discussions, and use of electronic resources, as >50% of respondents reported no improvement in these areas. In conclusion, this is the first report, to our knowledge, that describes a program developed by senior medical students to improve the experience of freshmen.

Patterns of TH1/TH2 cytokines predict clinical response in multiple sclerosis patients treated with glatiramer acetate.

The patterns of Th1/Th2 cytokines in relapsing-remitting multiple sclerosis were analyzed to evaluate their relevance as biomarkers of therapy response to glatiramer acetate (GA). Serum interferon-γ (IFN-γ), osteopontin and interleukin (IL)-2, IL-4, and IL-10 were measured in 19 relapsing-remitting multiple sclerosis patients treated with GA in a prospective study over 3 years. The quotient (IL-2 + IFN-γ)/(IL-4 + IL-10) was elevated in patients with relapses as compared to relapse-free patients after 12 (p = 0.04), 24 (p = 0.02) and 36 months (p = 0.04). Our study indicates that specific patterns of Th1/Th2 cytokines predict the response to GA therapy.

Arabic translation and adaptation of Critical Care Family Satisfaction Survey.

OBJECTIVE: To translate and adapt the Critical Care Family Satisfaction Survey (CCFSS), and test its validity and reliability for use in Saudi Arabia. SETTING: Seven hundred-bed tertiary care hospital in Saudi Arabia. PARTICIPANTS: Seventy-six adult relatives of patients who had been cared for in an intensive care unit for 24 hrs or more. INTERVENTIONS: The CCFSS, a battery of 20 items divided into five subscales, was translated into Arabic. After transfer of patients to regular inpatient units, interviewers administered the survey to their next-of-kin. Respondents ranked their satisfaction with each item on a 5-point Likert scale. MAIN OUTCOME MEASURES: Subscale scores were calculated as the average of the individual item scores. The total scale score was the sum of the subscale scores. RESULTS: The total scale and 'Information', 'Support', 'Comfort' and 'Assurance' subscales showed acceptable internal consistency (Spearman's correlation coefficient of the total score with each of the subscale scores = 0.52-0.81, P<0.01; Cronbach's alpha = 0.67-0.88). But the 'Proximity' subscale performed poorly (r=0.48, P<0.01; Cronbach's alpha = 0.36). Discriminant validity was tested with a Spearman's rank correlation matrix of the subscales, and ranged from weak between 'Support' and both 'Assurance' and 'Information' (r=0.80) to substantial between 'Information' and 'Proximity' (r=0.54) (P<0.01). CONCLUSION: This Arabic translation and adaptation of the CCFSS is a valid, reliable and feasible tool to evaluate family satisfaction in Saudi Arabian intensive care units.

Pulmonary hydatid cyst in a pregnant patient causing acute respiratory failure.

A 21-year-old primigravida, at 32 weeks of gestation, presented with acute onset of respiratory failure and circulatory shock. Chest imaging showed findings suggestive of ruptured hydatid cyst, which was confirmed by histology post-thoracotomy. Tissue cultures from the removed cyst grew Mycobacterium tuberculosis also. She was successfully managed in the intensive care unit and was then discharged home on antituberculosis medications in addition to albendazole after prolonged hospitalization and a need for chest tube for bronchopleural fistula. Acute respiratory failure and anaphylactic shock secondary to ruptured pulmonary hydatid cyst and superimposed pulmonary tuberculosis in a pregnant lady should be considered in patients living in endemic areas.

Clinical review: percutaneous dilatational tracheostomy.

As the number of critically ill patients requiring tracheotomy for prolonged ventilation has increased, the demand for a procedural alternative to the surgical tracheostomy (ST) has also emerged. Since its introduction, percutaneous dilatational tracheostomies (PDT) have gained increasing popularity. The most commonly cited advantages are the ease of the familiar technique and the ability to perform the procedure at the bedside. It is now considered a viable alternative to (ST) in the intensive care unit. Evaluation of PDT procedural modifications will require evaluation in randomized clinical trials. Regardless of the PDT technique, meticulous preoperative and postoperative management are necessary to maintain the excellent safety record of PDT.

Structured continuous objective-based assessment of resident's performance at point of care (SCOPA).

The assessment of the clinical performance of physicians-in-training is an important task. The critical care rotation is a mandatory rotation for most residency training programs and is designed to ensure the graduation of trainees who are able to initiate lifesaving management during medical emergencies. Ensuring that each resident fulfills the objectives of the rotation is of paramount importance. Unfortunately, the current assessment methods are subjective and suffer from many threats to validity and reliability that make the assessment inaccurate. In this review, the current assessment method is analyzed, and causes for inaccuracy are identified. A new model for assessment that is continuous, structured, objective-based and at the point of care (SCOPA) is proposed based on the best available assessment methods. Such a model might be useful for the assessment of trainee's performance in critical care as well as non-critical care rotations.

Protocol-driven vs. physician-driven electrolyte replacement in adult critically ill patients.

BACKGROUND: The intensive care unit is a dynamic environment, where high numbers of patients cared for by health care workers of different experiences and backgrounds might result in great variability in patient care. Protocol-driven interventions may facilitate timely and uniform care of common problems, like electrolyte disturbances. We prospectively compared protocol-driven (PRD) vs. physician-driven (PHD) electrolyte replacement in adult critically ill patients. PATIENTS AND METHODS: In the first month of the two-month study, potassium, magnesium, and phosphate levels were checked by a physician before ordering replacement (PHD replacement period). Over the second month, ICU nurses proceeded with replacement according to the protocol (PRD replacement period). We collected demographic data, admission diagnosis, number of potassium, magnesium, and phosphate levels done per day, number of low levels per day, number of replacements per day, time between availability of results to ordering replacement, time to starting replacement, post-replacement levels, serum creatinine, replacement dose, arrhythmias and replacement route. RESULTS: During the PHD replacement period, 43 patients meeting the inclusion criteria were admitted to the ICU, while 44 were admitted during the PRD month. The mean time (minutes) from identifying results to replacement of potassium, phosphate and magnesium was significantly longer with PHD replacement compared with PRD replacement (161, 187, and 189 minutes vs. 19, 26, and 19 minutes) (P<0.0001). The number of replacements needed and not given was also significantly lower in the PRD replacement period compared with the PHD replacement period (2, 4, and 0 compared with 9, 6 and 0) (P<0.05). No patients had high post-replacement serum concentrations of potassium, phosphate or magnesium. CONCLUSIONS: This study shows that a protocol-driven replacement strategy for potassium, magnesium and phosphate is more efficient and as safe as a physician-driven replacement strategy.

Therapy for ventilator-associated pneumonia: what works, what doesn't.

Ventilator-associated pneumonia is a common cause of morbidity and mortality in critically ill patients. Inappropriate initial antimicrobial therapy is associated with poor outcome. An initial aggressive strategy using broad-spectrum antibiotics based on the local distribution of pathogens, patient risk factors, and antimicrobial characteristics; followed by focused therapy based on microbiologic studies, will help minimize the chance of inappropriate therapy and the emergence of resistance.