Landmark trials Flashcards

Question

**CHEST (NEJM, 2012)** **"Crystalloid vs hydroxyethyl starch trial"** **"Hydroxyethyl starch or saline for fluid resuscitation in intensive care"**

Answer 1

Multicentre, RCT Ix effect of HES, esp in context of previously reported AEs on renal function **P -** Critically ill pts admitted to ICU (n = 7000) **I -** Voluven (6% HES; HES 130/0.4 ratio) **C** - NaCl 0.9% *Fluids given for all fluid resuscitaU d/c, death or 90days after randomisation* **O -** 1o - Death at 90days 2o - AKI, renal failure, Rx with renal-replacement therapy **Results:** * No significant difference in mortality (HES 18% vs NaCl 17%, RR HES 1.06, 95% CI 0.96 - 1.18, p = 0.26) * Significantly increased renal-replacement need in HES group (7% vs 5.8%, RR 1.21, 95% CI 1 - 1.45, p = 0.04) * HES associated with significantly more adverse events (5.3% vs 2.8%, p \< 0.001) ***_HES in critically ill patients was associated with a significantly higher incidence of AKI and requirement for RRT_***

Answer 2

Ix threshold for PRBC transfusion in hip # surgery **P -** \>50yo with h/o or RF for CV disease with Hb \>100g/L after hip fracture surgery (n = 2016) **I -** Restrictive transfusion strategy (Sx anaemia, Hb \>80g/L) **C -**Liberal transfusion strategy (Hb transfused to 100g/L) **O -** Death or inability to walk across a room without human assistance at 60-days **Results:** * There were no significant differences in mortality, functional performance or any outcome * Liberal transfusion (trigger Hb\<100) is no better than restrictive transfusion (trigger anemia symptoms or Hb \< 80)

Answer 3

Retrospective study looking at a military hospital in Afghanistan **P -** Trauma pts requiring transfusion (n = 896) **I -** TXA bolus 1g (rpted at clinical judgement by clinician) **O -** Mortality, VTE, **Results:** * TXA significantly reduces mortality in trauma (17% v 23%), esp. where massive transfusion is required * TXA group had significantly lower mortality, despite having more severe injuries * TXA was associated with an OR 7 for survival * Associated with increased incidence of PEs and DVTs though (overall roughly from ~0.5% to 2.5%) ?due to pts being sicker though * *

Answer 4

Ix whether decompressive craniectomy improves the functional outcome in patients with severe traumatic brain injury and refractory raised intracranial pressure **P -** Severe diffuse TBI and intracranial hypertension refractory to 1st tier therapies (n = 155) [December 2002 - April 2010] [able to be recruited up to 72hrs post admission to hospital] **I -** Bifrontotemperoparietal decompressive craninectomy * *C -** Standard care * Based on Brain Trauma Foundation guidelines: - 1st tier Rx - sedation, normal PaCO2, mannitol, hypertonic saline, NMBDs, EVD* *-2nd tier Rx - mild hypothermia 35oC), barbiturates* **O -** Extended Glasgow Outcome Scale score at 6months *(Original primary outcome = unfavourable outcome (composite of death, vegetative state, severe disabilityI at 6months post injury)* **Results:** * Decompressive craniectomy: * ↓ICP (p\<0.02) * ↓length of ICU stay (p\<0.001) * ↓ duration mechanical ventilation * BUT significantly higher chance of being dead/vegetative/severely disabled (odd ratio 2.21, 95% CI 1.14 - 4.26, p = 0.02) * Rates of death at 6months similar in both groups (19% craniectomy vs 18% usual care)

Answer 5

Multicentre, RCT **P -** Large AAA \>5.5cm diameter) (n = 1252) [years 1999 - 2004] **I -** EVAR **C -** Open AAA repair **O -** Rates of death, graft-related complications, re-nterventions **Results:** * Significant reduction in 30-day operative mortality in EVAR group (1.8% vs 4.3%, EVAR odds ratio 0.39, 05% CI 0.18 - 0.87, p= 0.02) * EVAR group had early benefit re: aneurysm-related mortality, but benefit lost by end of the study (partially due to fatal endograft ruptures) * No significant difference in rates of death from any cause by the end of the study (p = 0.72) * Rates of graft-related complications and reinterventions were higher with EVAR and new complications occurred up to 8yrs post randomisation \>\> contributing to higher overall costs

Answer 6

Multicentre RCT Endovascular coil vs craniotomy + clipping for subarachnoid aneurysm **P -** Ruptured intrcranial aneurysms across 42 neurosurgical centres (n = 2143) **I -** Endovascular coiling **C -** Neurosurgical clipping \*\* Note - not all aneurysms are amendable to coiling e.g. wide neck **O -** 1o - Death or dependent at 1yr (modified Rankin scale 3 - 6) 2o - rebleeding from Rx aneurysm, risk of seizures **Results:** * In pts with ruptured intracranial aneurysms amenable to both clipping and coiling, _coiling_ leads to a greater chance of survival free of disability at 1 year (23.5% vs 30.9%, p = 0.0001) * Survival benefit with coiling continues for at least 7 years * Risk of epilepsy lower in coiling * **BUT** Rebleeding rare, but more common with coiling

Answer 7

International, multicentre Randomised, double-blind, placebo controlled trial **P -** PPH post NVD or LSCS (n = 20,000) **I -** TXA 1g IV (2nd dose 1g TXA given if bleeding continued after 30mins or re-bleed within 24hrs) **C -** Placebo + usual care **O -** Risk of death from PPH **Results:** * Significantly reduced risk of death from PPH in TXA (1.5% vs 1.9%, RR 0.81, 95% CI 0.65 - 1, p = 0.045), especially in women Rx within 3hrs of delivery (1.2% vs 1.7%, RR 0.69, 95% CI 0.52 - 0.91, p = 0.008) * Hysterectomy not reduced in TXA group (RR 1.02, 95% CI 0.8 - 1.07, p = 0.84) * The composite primary endpoint of death from all causes or hysterectomy was not reduced with TXA ( 5·3% vs5·5%, RR 0·97, 95% CI 0·87-1·09; p=0·65). * Adverse events (including thromboembolic events) did not differ significantly in the tranexamic acid versus placebo group. **Interpretation:** * *Tranexamic acid reduces death due to bleeding in women with post-partum haemorrhage with no adverse effects.* * *When used as a treatment for postpartum haemorrhage, tranexamic acid should be given as soon as possible after bleeding onset.*

Answer 8

International, multicentre, RCT **P -** Pt undergoing major abdominal surgery and at increased risk of complications (n = 3000) **I -** Restrictive IV regimen (designed for net zero fluid balance. 5ml/kg induction and intraop, no pre-op fluid. 0.8ml/kg post-op infusion) **C -** Liberal IV regimen (crystalloid 10ml/kg during induction then 8ml/kg to end of surgery; post-op 1.5ml/kg infusion for at least 24hrs) \*\* Both arms of IV therapy for 24hrs post surgery **O -** 1o - Disability-free survival at 1yr 2o - AKI at 30days, renal-replacement therapy at 90days, composite of septic complications, surgical-site infection and death **Results:** * No significant difference in 1yr disability-free survival (81.9% restrictive vs 82.3% liberal, p = 0.61) * Significantly increased rate of AKI in restrictive fluid group (8% vs 5%, p \<0.001) * Significantly increased rate of surgical site infection (16.5% vs 13.6%, p = 0.02) and renal-replacement therapy (0.9% vs 0.3%, p = 0.048) in restrictive fluid group * Non-significant increase in septic complications/death in restrictive group (21.8% vs 19.8%, p = 0.19) **CONCLUSIONS** *"Among patients at increased risk for complications during major abdominal surgery, a r**_estrictive fluid regimen was not associated with a higher rate of disability-free survival_** than a liberal fluid regimen and was associated with a **_higher rate of acute kidney injury._***

Answer 9

Multicentre, 2-arm parallel group, randomised trial, blinded post-op care **P -** Elective open or laparoscopic bowel surgery for benign or malignant pathology (n = 1350) **I -** Dexamethasone 8mg at induction **C -** Standard care (no antiemetics) **O -** 1o - PONV (within 24hrs) 2o - Vomiting within 72 and 120hrs, use of antiemetics and PONV at 24, 72, 120hrs rated by pt, fatigue and QoL at 12hrs or discharge and at 30days, time to return to oral intake, length of hospital stay, adverse events **Results:** * Significantly less vomiting within 24hrs in dex group (25.5% vs 33%; NNT 13, 95% CI 5 - 22, p = 0.003) * Significantly less rescue anti-emetics in dex group (39.3% vs 51.9%, NNT 8, 95% CI 5 - 11, p \< 0.001); reduction in antiemetics remained up to 72hrs * No increase in complications with dex use

Answer 10

Multicentre, double blind, 2x2 factorial trial **P –** pt undergoing CABG at risk of major complications (age \>70yo, LV impairment, concomitant valvular or aortic surgery, repeat surgery and medical comorbidities – COPD/CKD/obesity/PVD/pulm HTN; eligible if not taking aspirin or if aspirin ceased for at least 4days pre-op) **I –** aspirin given prior to surgery (100mg) **C –** Placebo **O –** 1o - composite of death or thrombotic events (non-fatal MI, CVA, PE, renal failure, bowel infarction) within 30-days post-op 2o - blood transfusion, re-operation, respiratory failure, length of stay **Results:** * No clinical or statistical differences found (19.3% vs 20.4% asp vs placebo), RR 0.94 (95% CI .08 – 1.12, P = 0.55), ARR 1.12% (95% CI 2.29 – 4.54%, P = 0.55) * 2o outcomes: No statistically significant difference in any of the individual outcomes of composite 1ooutcome * More plt transfusion on day 1 in aspirin group (15 vs 13%, P = 0.23) * More PRBC transfused from day 2 to discharge in aspirin group (18.1% vs 16.1%, P = 0.08) * No difference in ICU stay, hospital stay, duration of mechanical ventilation

Answer 11

Multicentre, double blind, 2x2 factorial trial **P -** High risk patients undering CABG (n = 4631) **I -** TXA (50 - 100mg/kg) **C -** Placebo **O -** 1o - composite of death and thrombotic complications (non-fatal MI, CVA, PE, renal failure, bowel infarction) within 30days 2o - blood transfusion, re-operation, respiratory failure, length of stay **Results:** * No significant difference in composite of death/thrombotic complications (18.1% TXA vs 16.7% placebo, p = 0.22) * Significantly reduced: * Major haemorrhage and cardiac tamponade requiring re-operation in TXA group (1.4% vs 2.9%, p =0.001) * PRBC within 24hrs in TXA group (31% vs 49%, p \<0.001) * Significantly increased perioperative seizures in TXA group (0.7% TXA vs 0.1%, p = 0.002)

Landmark trials Flashcards

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