NONSEDA Trial Summary: Sedation in Critically Ill Intubated Patients

NONSEDA Trial nonsedation in mechanically ventilated

2020 NONSEDA TRIAL M Nonsedation or light sedation in critically ill, mechanically ventilated patients Investigator-initiated, randomised, clinical, parallel-group, multinational, superiority trial . a 5 Objective: To assess whether in critically ill, mechanically ventilated patients, does a strategy of no sedation, as compared with light sedation with daily sedation breaks, impact day 90 mortality. 192 patients Patients 18 years of age, who underwent endotracheal intubation within 24 hours before screening & were expected to receive mechanical ventilation for more than 24 hours. Nonsedation group (N = 349) Sedation group (N = 351) | PRIMARY OUTCOME 42.4 90 day mortality % Diff. 5.4; 95% CI, -2.2 to 12.2; P=0.65 SECONDARY OUTCOME Days until death Diff. 1; 95% CI, -2 to 5 12 13 ICU days Diff. – 1; 95% CI, -7 to 4 Conclusion: Among mechanically ventilated ICU patients, mortality at 90 days did not differ significantly between those assigned to a plan of no sedation and those assigned to a plan of light sedation with daily interruption. H Olsen et al. NEJM 2020; 382:1103-1111

ESETT Trial Summary: Anticonvulsant Medications for Status Epilepticus

ESETT Trial anticonvulsants status epilepticus

2019 ESETT TRIAL Randomized trial of three anticonvulsant medications for Status Epilepticus Investigator-initiated, blinded, randomized controlled trial Objective: To investigate whether in patients with status epilepticus who have been treated with benzodiazepines, is Levetriracetam, Valproate or Fosphenyoin more likely to lead to an absence of seizures and improved responsiveness at 60 minutes 384 patients Patients of age > 2 years treated with generally accepted cumulative dose of BZD’s for generalised convulsive seizures lasting >5 mins & continued to have persistent or recurrent seizures at least 5 mins after last dose of BZD & no more than 30 mins after the last dose. Levetiracetam (N=145) Fosphenytoin (N=118) Valproate (N=121) PRIMARY & SECONDARY OUTCOMES Absence of seizures & improving responsiveness at 60 min Levetiracetam, 95% CI, 39 to 55 Fosphenytoin, 95% CI, 36 to 54 Valproate, 95% CI, 38 to 55 45 46 Admission to ICU % 60 59.3 58.7 Life threatening hypotension within 60 minutes % 0.7 3.2 1.6 Conclusion: In the context of benzodiazepine-refractory convulsive status epilepticus, the anticonvulsant drugs levetiracetam, fosphenytoin, & valproate each led to seizure cessation & improved alertness by 60 minutes in approximately half the patients, and the three drugs were associated with similar incidences of adverse events. J Kapur et al. NEJM 2019, 381-2103-13

PEPTIC Trial Summary: PPI vs. H2 blockers for Stress Ulcers in Intubated Patients

PEPTIC Trial stress ulcers PPI H2 blockers

2020 PEPTIC TRIAL Effect of stress ulcer prophylaxis with Proton pump inhibitors vs Histamine-2 receptor blockers on in-hospital mortality among ICU patients receiving invasive mechanical ventilation Pragmatic, open-label, cluster randomised crossover design trial Objective: To compare in-hospital mortality rates using PPIs vs Histamine-2 receptor blockers (H2RBs) for stress ulcer prophylaxis. 26828 Inclusion criteria: Participants 18 years of age requiring invasive mechanical ventilation within 24 hours of ICU admission & those with diagnosis of upper gastrointestinal bleeding were excluded. patients PPl group (n=13436) H2RB group (n=13392) PRIMARY OUTCOME 18.3 90 day in-hospital mortality % RR 1.05; 95% CI, 1.00 to 1.10; P=0.054 17.5 SECONDARY OUTCOME upper GI bleeding % 1.3 1.8 RR 0.73; 95% CI, 0.57 to 0.92; P=0.009 0.3 Clostridium difficile infection % RR 0.74; 95% CI, 0.51 to 1.09; P=0.13 0.43 Conclusion: Among ICU patients requiring mechanical ventilation, a strategy of stress ulcer prophylaxis with use of proton pump inhibitors vs histamine-2 receptor blockers resulted in hospital mortality rates of 18.3% vs 17.5%, respectively, a difference that did not reach the significance threshold. P Young et al. JAMA. 2020;323(7):616-626

VAM-IHCA Trial Summary: Vasopressin and Methylprednisolone on ROSC after Cardiac Arrest

VAM IHCA Trial, vasopressin, methylprednisolone

2021 VAM-IHCA TRIAL M Effect of Vasopressin and Methylprednisolone vs Placebo on Return of Spontaneous Circulation in Patients with In-Hospital Cardiac Arrest Multicenter, randomized, double-blind, placebo-controlled trial Objective: To determine whether the combination of vasopressin and methylprednisolone administered during in-hospital cardiac arrest improves return of spontaneous circulation. 512 patients Inclusion criteria: Patients >18 years of age with in-hospital cardiac arrest and received at least 1 dose adrenaline Vasopressin + methylprednisolone group (n=237) Placebo group (n=264) PRIMARY OUTCOME 42 Return of spontaneous circulation % RR 1.30; 95% CI, 1.03 to 1.63; P=0.03 SECONDARY OUTCOME 9.7 Survival % RR, 0.83; 95% CI, 0.50 to 1.37; P=0.48 7.6 Favorable neurologic outcome% RR 1.00; 95% CI, 0.55 to 1.83; P >0.99 7.6 Hyperglycemia % Conclusion: Among patients with in-hospital cardiac arrest, administration of vasopressin and methylprednisolone, compared with placebo, significantly increased the likelihood of return of spontaneous circulation. LW Andersen et al. JAMA 2021;326(16):1586-1594

CHECK-UP Trial Summary: Ramped vs Sniffing Position for Intubation

CHECK UP trial endotracheal intubation position

2017 CHECK-UP: POSITION- Ramped position vs Sniffing position during endotracheal intubation of critically ill adults 2 x 2 factorial design,randomised, multicentre,pragmatic trial 9 5 Objective: To evaluate the reduction in incidence of oxygen desaturation in ramped position as compared to sniffing position in emergency intubation in critically ill ICU patients 260 patients Patients >18 yrs undergoing endotracheal intubation by critical care or pulmonary fellows in the medical ICU Ramped position (n=130) Sniffing position (n=130) PRIMARY OUTCOME Median lowest arterial 02 saturation % P=0.27 SECONDARY OUTCOME 25.4 % Incidence of grade III or IV intubatio view P=0.01 11.5 12.3 % Incidence of difficult intubation P= 0.04 4.6 76.2 Rate of intubation on the 1st attempt % P=0.02 85.4 Conclusion: The Ramped position did not improve oxygenation during endotracheal intubation of critically ill adults as compared with the sniffing position but did increase the difficulty of intubation and the likelihood of repeated attempts. MW Semler et al. Chest 2017, 152(4):712-722

ATACAS Trial Summary: Tranexamic Acid in Coronary Artery Surgery

ATACAS Trial aspirin and tranexamic acid

2017 ATACAS TRIAL: Tranexamic Acid in patients undergoing coronary artery surgery Multicenter,2×2 factorial design, double-blind, randomized controlled trial Objective: To evaluate death risk and thrombotic complications with TXA among at-risk patients undergoing coronary artery surgery. 4662 Inclusion criteria: Patients >18 years of age undergoing elective coronary artery surgery either on or off pump & at increased risk of major complications patients OMEO TXA group (n=2329) Placebo group (n=2333) PRIMARY OUTCOME 16.7 Composite of Death or Thrombotic events % RR 0.92; 95% CI 0.81 to 1.05; P=0.22 18.1 SECONDARY OUTCOME 1.4 Reoperation due to major hhg or cardiac tamponade P=0.001 2.8 37.9 Blood products administered % P<0.001 54.7 0.7 Seizure % RR 7.62; 95% CI 1.77 to 68.71; P=0.002 0.1 Conclusion: TXA was associated with a lower risk of bleeding post-op & was not associated with increased risk of death or thrombotic effects. Miles et al. NEJM.2017,376:136-148

MIDAS Trial Summary: Midodrine for Vasopressor Weaning

MIDAS Trial Midodrine

2020 MIDAS TRIAL: Effect of midodrine versus placebo on time to vasopressor discontinuation in patients with persistent hypotension in the intensive care unit Multi-centre, randomised, double-blind, placebo-controlled trial Objective: To investigate whether the administration of midodrine, an oral al-adrenergic agonist, as adjunct to standard treatment shortens the duration of intravenous vasopressor requirement 132 Hypotensive patients >18 years of age requiring single-agent intravenous vasopressor treatment and unable to be liberated from vasopressors for at least 24 hours. patients Midodrine (n=66) Placebo (n=66) PRIMARY OUTCOME 23.5 Time from drug initiation until discontinuation in hours) Diff 1; 95% CI, -10.4 to 12.3; P=0.62 22.5 SECONDARY OUTCOME Time to ICU discharge readiness (in days) Diff 0; 95%CI, -1 to 1; P=0.64 lind ICU length of stay (in days) Diff 0; 95%CI, -0.5 to 0.5; P=0.46 Conclusion: Midodrine did not accelerate liberation from intravenous vasopressors and was not effective for the treatment of hypotension in critically ill patients as compared to placebo. P Santer et al. Intensive Care Medicine DOI:10.1007/s00134-020-06216-X

EAT-ICU Trial Summary: Early Goal-Directed Nutrition in ICU Patients

eat icu trial nutrition in critically ill

2017 EAT-ICU TRIAL: Early goal-directed nutrition versus standard of care in adult intensive care patients Single centre, blinded, randomised controlled trial Objective: To evaluate the effects of early goal-directed nutrition (EGDN) vs. standard nutritional care in adult ICU patients. 203 Inclusion criteria: Acutely ICU admitted, mechanically ventilated patients, aged >18 yrs with a central venous catheter (for PN if required) expected to stay >3 days patients Early goal-directed nutrition (n=102) Standard nutrition (n=101) PRIMARY OUTCOME 22.9 Mean PCS score (Physical quality of life at 6M) Diff 0.0; 95% CI -5.9 to 5.8; P=0.99 23.0 SECONDARY OUTCOME Mortality at 6M % 34 Mortality,rates of organ failures, serious adverse reactions or infections in the ICU, length of ICU or hospital stay, or days alive without life support at 90 days did NOT DIFFER much between the two groups Conclusion: EGDN did not appear to affect physical quality of life at 6 months or other important outcomes as compared to standard nutrition care in acutely admitted, mechanically ventilated, adult ICU patients. MJ Allingstrup et al. Intensive Care Med. 2017 Nov, 43(11):1637-1647

EPICC Trial Summary: Intensive Physical Rehabilitation in Critically ill

EPICC Trial PT in critically ill patients

2017 EPICC TRIAL Intensive versus standard physical rehabilitation therapy in the critically illl parallel-group, assessor-blinded, randomized controlled trial Objective: To determine improvement in long-term clinical outcomes with Increased intensity ICU-based physical rehabilitation therapy as compared with standard therapy. 308 Inclusion criteria: Patients >18 years who received 48 hours of either invasive or non-invasive ventilation patients Intensive physical rehabilitation (n=150) Standard physical rehabilitation (n=158) PRIMARY OUTCOME 6M Physical Component Summary(PCS) measure of SF-36 % Intensive care: PCS Mean (SD)= 37 (12.2) Standard care: PCS Mean (SD)= 37 (11.3) Diff -1.1; 95% CI -7.1 to 5.0 SECONDARY OUTCOME Mental Component Summary measure of SF-36 % Diff -0.4; 95% CI -6.5 to 5.7 Median ICU stay-alive at discharge (in days) 13 Diff 0.3; 95% CI-4.1 to 4.8 Conclusion: ICU-based physical rehabilitation did not appear to improve physical outcomes at 6 months compared with standard physical rehabilitation. Se Wright et al. Thorax.BMJ 2018,73:213-221

DREAMS Trial Summary: Dexamethasone for Post-op Nausea and Vomiting

DREAMS Trial summary: Dexamathasone for post op nausea and vomiting

2017 DREAMS TRIAL Dexamethasone vs standard treatment for postoperative nausea and vomiting (PONV) in gastrointestinal surgery Pragmatic, blinded, multicentre,randomised controlled trial Objective: To determine reduction in PONV by preoperative Dexamethasone in patients undergoing elective bowel surgery & its association with other measurable benefits during recovery from surgery. 1350 patients Inclusion criteria: Adults over 18 years undergoing elective open or laparoscopic bowel surgery for malignant or benign pathology. Dexamethasone (n=674) Standard care (n= 676) PRIMARY OUTCOME 25.5 Vomiting within 24 hrs after surgery % RR 0.77; 95%CI 0.65 to 0.92; P=0.003 SECONDARY OUTCOME 39.3 On demand additional post-op antiemetics % RR 0.76, 95%CI 0.67 to 0.85; P<0.001 NNT=8; P<0.001 51.9 % Mortality within 30 days P=1 Conclusion: The administration of Smg Dexamethasone in addition to standard antiemetic care reduces the incidence of nausea & vomiting without increasing adverse events The DREAMS trial Collaborators, BMJ 2017, 357.j1455