Cardiac arrest - Therapeutic Hypothermia
2002 NEJM: Patients with witnessed shockable arrest; 137pts with targeted hypothermia to 32-34C over 8h then held at that temp for 24h then passively re-warmed over 8h. Cooling performed within 2h of event. However, a large number of patients in control group developed fever. There was also no blinding.
Then NEJM Nov 17 2013 published a study with 950pts over 3 years. 80% vfib, 12% asystole, 8% PEA and randomized to 33 or 36 for 28h and then fever reduction for 72h. After 72h, a neurologist blinded to initial treatment allocation recommended withdrawal or continued care. Withdrawal recommended only for known predictors of a terrible outcome: refractory SE, GCS 1-2 with bilateral absence of N20peak on median nerve SSEP. CPC>2 or Rankin>2 was defined as severe disability. There was no difference between the two groups even in the shockable group.
2013 JAMA, 100 patients with bacterial meningitis were randomized to 32-34C or standard care and this was stopped early for a 20% absolute risk increase in mortality in treatment group.
Cardiac arrest - Prognosis
Pupillary reaction to light has a false positive rate of 0-31% at day 1 and 0% at day 3. Absence of corneal reflexes and posturing show a similar trend.
Review of Lancet - perfect specificity for poor neurological outcome is d3 absent motor and pupillary response plus abnormal SSEP (stimulation of median nerve with absent brain response). Bilateral absent SSEP is poor neurological prognosis from NEJM 2009. Nothing is good for predicting neurological outcomes d1-3 especially given analgesia, sedation, and hypothermia.
Cardiac arrest in ICU - Prognosis
Observational trial of 50 000 arrests showed an overall survival to hospital discharge of 16%. Only 10% of patients requiring vasopressors prior to the arrest survived to discharge and only 4% overall were discharged home. Among those with PEA/asystole despite pressors, only 1.7% were able to perform their own activities of daily living at the time of discharge. People with ventricular fibrillation or tachycardia not requiring pressors prior to arrest did much better: 40% survived, 20% went home, and 17% had good neuro outcomes.
25% excess salt and fluid intake
25% noncompliance with medications
16% adverse medication effects (e.g. new CCB, NSAID, steroids, glitazones, ethanol, new anti-arrhythmic)
34% medical (ischemia, PE, HTN, valve dysfxn, arrhythmia, sepsis, infection, renal failure, thyroid, anemia)
Bblockers with proven mortality benefit in HF:
Carvedilol (COPERNICUS). Superior to metoprolol for chronic treatment (NEJM 344:1651, 2001; Lancet 362:7, 2003)
Bisoprolol - CIBIS trial Lancet 353:9, 1999
Metoprolol succinate - MERIT-HF study JAMA 283: 1295, 2000)
enalapril: SOLVD, captopril: SAVE improve survival and symptoms in LV systolic dysfxn
Losartan: ELITE Lancet 355:1582, 2000
Valsartan: Val-HEFT NEJM 345:1667, 2001
Candesartan: Lancet 362:772, 2003
Hydralazine and nitrates improve survival in patients with HF (NEJM 314:1547, 1986)
In African Americans, addition of hydralazine and nitrates to Bb and ACEi reduces mortality (A-HEFT NEJM 351:2049, 2004)
Spironolactone improve survival and decrease hospitalizations in NYHA III-IV HF (RALES NEJM 341:753, 1999)
Eplerenone (no hormonal side effects) reduces mortality in HF from acute MI (EPHESUS: NEJM 348:1309, 2003)
CAST and the STITCH trial showed that revascularization with bypass surgery versus medical therapy in patients with EF < 35% improves death from cardiac causes, hospitalizations, and NYHA class; but not overall mortality.
Myocarditis, prednisone has shown to increase EF by 5% but only if there is cellular infiltrate on biopsy.
Felker et al NEJM 2011 DOSE trial showed no difference between bolus and continuous infusion of diuretics. High dose (double outpatient dose) seemed to improve global assessment of symptoms. No survival benefit, creatinine, readmission, or cardiac performance with diuretics.
V-HEFT trial compared hydra + isosorbide vs prazosin vs placebo and hydra + isosorbide showed a mortality benefit.
Nesiritide was studied on O'Conner NEJM 2011 and shown that it might improve dyspnea but no effect on mortality or readmission. However, it seems to lower filling pressures more than nitroglycerine or diuretics with an improvement in cardiac output.
ACEi does everything. The addition of ARB is debated. Val-HEFT showed that the addition of valsartan to ACEi decreased hospitalizations but did not improve mortality - leading to increased mortality when used in conjunction with Bb. VALIANT showed that ARB are not superior to ACEi and that the combination of the two led to increased hypotension and renal dysfunction. CHARM trial, however, showed that the addition of candesartan to ACEi decreased cardiovascular death and hospital admission for CHF.
Spironolactone was shown in the NEJM-RALES in 1999 to improve mortality. The exclusion criteria was Cr > 2.5. However, after its publication, Juurlink NEJM 2004 summarized many case series of deaths from hyperkalemia. Eplerinone can reduce mortality after MI in patients with LV dysfunction (EF < 30%) who are also on ACEi and Bb (EMPHASIS-HF).
UScarvedilol (NEJM 1996) showed survival benefit with carvedilol in low EF. MERIT-HF (Lancet 1999) showed a survival beneft with metorpolol -XL. Copernicus trial in 2001 showed a benefit with carvedilol in very low EF.
DIG-NEJM 336:525, 1997 showed reduction in hospitalizations and symptoms with digoxin.
Defibrillator improves mortality especially with LVEF < 35% in MADDIT 1 & 2, MUST, SCD-HEFT. In patients with depressed LVEF with symptoms and QRS > 120ms and LBBB, CRT improves LVEF, reduces MR, reduces dyspnea, and reduces hospitalizations according to the COMPANION study. Mortality was only reduced in CRT plus AICD.
REMATCH trial demonstrated improved survival in late class IV heart failure.
PA-cath in heart failure did not have a mortality benefit but led to better hemodynamics in ESCAPE trial.
50% of STEMI presented with vfib arrest. Up to 33% of confirmed MI did not have chest pain. This subgroup had 3x mortality due to diagnostic uncertainty. STE can evolve into Qw within 6h in 50% of patients. Based on a MRI study in 2004, 29% of transmural MI did not have Qw and 28% of subendocardial MI did have Qw. High lateral MI is commonly silent on EKG and can lead to anterolateral papillary muscle rupture. Normal ECG with flash pulmonary edema should prompt the differential of high lateral MI.
Treating a STEMI patient presenting within 3h but could not undergo PCI within 1h of first medical contact with tenecteplase and antithrombotics has similar efficacy as PCI - STREAM.
ISIS-2 trial showed ASA reduces mortality by 23%. Clopidogrel adds to mortality reduction. Anticoagulation should be used for at least 48h. LMWH may be better than UFH in reducing nonfatal MI, and urgent revascularizations. However, LMWH increases risk of non-fatal bleeds.
Use of fibrinolytic therapy saved 49/1000 lives if ECG showed LBBB, 37/1000 lives if anterior STE, and 8/1000 lives if inferior STE. However, 14/1000 patients harmed if STd. The amount of benefit correlates with the number of leads with STE; there is little benefit if only 2-3 leads have STE. Lytics should be given if PCI cannot be achieved in 120min of first medical contact. The mortality benefit to PCI is nullified when time to delay to primary PCI is > 2h. TRANSFER-AMI trial showed that there is still a benefit for rescue PCI within 6h post-lytics. Best candidates for transfer include >4h after symptoms, high risk lesions, shock, high bleeding risk.
Patients presenting with STEMI and cardiogenic shock benefit from emergent revascularization (PCI or CABG) compared to lytics according to the SHOCK trial. Most do not present with hypotension but develop this within 24h. 25% of this group did not have pulmonary congest on exam. 30d mortality between medical arm and revascularization was no different unless age < 75 but there was significant difference at 60d. ~50% mortality at 30d.
IABP-SHOCK2 trial in NEJM 2002 does not support the use of IABP in acute MI with shock.
ACEi should be started in MI if EF<40%, DM, CKD, HTN.
RV infarction is seen in 30% of patients with inferior MI and clinical significant in 10%.
Mechanical complications of MI: rupture muscular wall (RAP, RVd, PAd, and PAWP all elevate within 5mmHg of each other), hemorrhagic pericarditis (similar to wall rupture but from lytics), RV infarction (elevated RAP, RVm, PAWP), VSD (5mmHg step up in PaO2 from RA to RV, tall V waves on wedge), papillary muscle rupture of posterolateral leaflet (tall V waves on wedge, murmur usually absent due to equalization of pressures).
For NSTEMI, plavix reduces risk of composite end point y 2.1% in CURE trial, NEJM 2001. 600mg should be given as loading per CURRENT OASIS 7, NEJM. Plavix should be given before or at the time of PCI. GP2b3a before or at the time of PCI or prasugrel at the time of PCI.
In NSTEMI patients with pulmonary edema by exam or CXR, CCB worsens outcomes in 1980s study. ACEi should be given within 24h in these patients unless hypotension or contraindication.
NSTEMI patients may benefit from cath if there is baseline troponin elevation or ST changes. No benefit in low risk patients. Only those with high risk according to TIMI and GRACE benefited from early intervention, not low or moderate - Mehta NEJM 2009.
Anterior MI associated with Type II Mobitz and inferior MI is associated with Type I Mobitz.
Lower doses of adenosine should be used for patients on dipyridamole, heart transplant, or central line. Denervated heart is hypersensitive to sympathomimetics, cholinergics, and adenosine (3-6x higher sensitivity). Dipyridamole potentiates the effects of adenosine by inhibiting its uptake by blood and other vasculature increasing its effects on the heart and platelets.
Dopamine increases renal blood flow and urine output but when used routinely does not affect renal function - ANZICS trial in Lancet.
Vasopressin was not used in patients with myocardial ischemia in the VASST trial NEJM 2008. Low doses increases splanchnic blood flow and urine output.
Norepi is a good choice in cardiogenic shock according to SOAP II trial.
Penetrating trauma patients benefit from no fluid resuscitation - Mattox NEJM 1994.