On the 21st of February this year we mentioned a paper by Sharifi et al. who introduced a new concept of 'Safe Dose Thrombolysis'. Background is the fact that for most patients, e.g. intermediate risk pulmonary embolism (PE), thrombolysis is not recommended due to the risk of bleeding. The question though remained wether intermediate risk patients actually also would benefit of thrombolysis in terms of outcome. In the recent NEJM now a trial is presented where the investigators focused on exactly this so called 'intermediate risk' group of patients. They randomized 1005 patients with PE who had right ventricular dysfunction on echocardiography or computed tomography, as well as myocardial injury as indicated by a positive test for cardiac troponin I or troponin T. The one group received tenecteplase and heparin, the other only heparin. Result: Thrombolysis prevented hemodynamic decompensation and death... but at the same time increased the risk for major hemorrhage and stroke. What a dilemma! That's where I feel 'Safe Dose Thrombolysis' might be interesting to look at. Now there's a good topic for your next publication in the NEJM, go for it! (and please don't forget to mention us for the great idea ; ) Meyer G et al. N Engl J Med 2014; 370:1402-1411 Sharifi M et al. Clin Cardiol. 2014 Feb;37(2):78-82 Most of us are aware of the medical leaflet warning that beta blockers in bronchospastic disease should be avoided or at least be given with great caution due to the risk of increased airway resistance. An interesting question therefore is, whether beta blockers prescribed in COPD patients with acute myocardial infarction (AMI) also benefit of their effect and if this also affects survival. Quint et al. have looked into this topic by performing a retrospective study including 1063 COPD patients, who experienced their first AMI. 55.1% of these patients were never prescribed a beta blocker throughout the study period, 23% were on beta blockers before and 21.9% were prescribed a beta blocker during their hospital admission for AMI. Patients started on beta blocker during their hospital admission showed substantial survival benefits compared to patients who were not prescribed any beta blockers. Patients taking beta blockers before their first myocardial infarction also showed a substantial survival benefit! Taking into the account these results and the increasing evidence that beta blocker are actually safe in COPD patients suggests that beta blockers should be used more widely in patients at risk for AMI. At least we should not be too worried to prescribe them. Quint J K et al. BMJ 2013;347:f6650 Dransfield M T et al. Torax 2008;63:301-305 As published in the New England Journal the ALBIOS trial has already received a lot of attention and was also one of the hot topics at the ISICEM in Brussels last week. So what’s the story. First there is the original article published in the recent NEJM. Gattinoni et al. have looked into the potential advantages in giving 20% albumin and cristalloid solutions to hypoalbuminic patients with severe sepsis compared to cristalloid solutions only. In the albumin group they aimed for a serum albumin concentration of 30g/L (a number hardly ever seen in any ICU patient) until discharge from the ICU or 28 days after randomization. 1818 patients were included and to make things short: The trial found no difference in 28-day mortality (primary outcome), 90-day mortality (secondary outcome), or any other relevant clinical endpoint (number of patients with organ dysfunction, degree of dysfunction, length of stay in ICU and the hospital). So far for the original article. But now there is also this wonder-some supplementary appendix where the group has performed an unplanned subgroup analysis in septic shock patients only where a significant difference in the 90-day mortality was found - in favor for albumin. Indeed there is a lower number of deaths in the albumin group, but not in the p value when adjusted for clinically relevant variables. It might also be interesting to note that the 90-day mortality was a secondary endpoint and no subgroup analysis was performed of 28-day mortality among patients with septic shock. My personal view on this topic is that the original article and the supplemental appendix provide no good reason to favor albumin in the treatment of septic patients in general. The evidence provided to support the application of hypertonic albumin in septic shock patient is also not very convincing. In regards of the SAFE study from 2004 the use of albumin will remain controversial and it will be interesting to see further trials upcoming in this field. It is also worthwhile remembering that albumin remains reasonably expensive and as Prof. Takala, Bern Switzerland, mentioned in Brussels last week: the money saved on avoiding unnecessary albumin infusions might be better invested in other ICU resourced proven to improve patient outcome. Comments? Gattinoni L et al. N Engl J Med March 18, 2014 Gattinoni L et al. N Engl J Med March 18 2014: Supplemental Appendix SAFE study. N Engl J Med 2004; 350:2247-2256 In this recently published Brief Report in the Journal of Academic Emergency Medicine Patanwala et al. looked retrospectively at first pass intubation success by comparing Ketamine to Etomidate. The final cohort included 2098 patients and even after adjusting for potential confounders there was no difference in success rates between the two drugs. In regards of recent discussions on the safety of Etomidate (e.g. adrenal suppression) this study seems to be another puzzle piece favoring other induction agents than Etomidate. Looking at recent publications on paralyzing agents and personal experience I feel that Ketamine and Rocuronium is a favorable combination for rapid sequence inductions in the ICU... what do you think? Patanwala A et al.Academic Emergency. 2014 Feb Curley J et al. Critical Care. 2011,15:190 Marsch SC et al.Crit Care. 2011 Aug 16;15(4):R199 Since the FDA’s approval of Propofol in 1993 it has become one of the most important drugs used in anaesthesia. It’s properties (short induction time, short half life) have made it an ideal agent for the use in theatre. Also in critical care Propofol was increasingly used for long term sedation and it’s anti-epileptic properties have been welcomed by intensivists treating patients with status epilepticus. In 1992 T.J. Parke et al. published for the first time an article in the BMJ describing 5 children who developed increasing metabolic acidosis, brady-arrhythmia and progressive myocardial failure while sedated with Propofol - today often referred as the Propofol Infusion Syndrome (PRIS). This rare complication shows a complex pathophysiology which is still not fully understood and still continues to be controversially discussed. While initially described in children and traumatic brain injury it is also increasingly reported in other critically ill patients. If you are interested in some background information on this syndrome this recent case report by Mayette et al., published in the Annals of Intensive Care, provides an interesting insight in this topic. Parke et al. BMJ. 1992;305:613 Mayette M. et al. Ann Intensive Care. 2013 Sep 23;3(1):32 Take Home Message: Risk factors for PRIS appear to be...
Queshi at al. have published a nice retrospective cohort study in order to answer the question if you should restart anticoagulation in patients with atrial fibrillation (AFib) after an event of gastrointestinal bleeding (GIB). If yes, will I harm the patient by doing so and when should I restart anticoagulation? In five years (2005-2010) 1329 patients developed major GIB. In 49.1% of these patients Warfarin was restarted and this was associated with decreased thromboembolism and reduced mortality. They were able to show that restarting Warfarin after 7 days was not associated with increased risk of GIB, but also reduced risk for thromboembolism and death compared to resume after 30 days of interruption. So, according to these data it seems safe to restart anticoagulation in these patients 7 days after a major GI bleed... and you even seem to do something good for your patient! Qureshi et al. Am J Cardiol. Nov 2013 Already years ago it has been noticed that stress and severe injury results in insulin resistance among ICU patients. This also occurs in patients who had no diabetic problems before an insult. Van den Berge et al. therefore postulated that an intensive glucose control in ICU patients would be of benefit. And indeed, in 2001 they published the well known article on intensive insulin therapy in critically ill patients. They showed that a tight glucose control results in reduced morbidity and mortality (by 42%) among ventilated, critically ill patients in surgical intensive care units (1548 patients included). Unfortunately though some clinical trials since have failed to reproduce this benefit of tight glucose control. A meta analysis in JAMA 2008 looked at 28 randomized controlled trial with a total of 8432 patients and found that tight glucose control was not associated with significantly reduced hospital mortality but an increased risk of hypoglycemia. The multinational NICE-SUGAR trial, including 6104 patients, finally made an end to tight glucose control on most ICU’s around the world. Against expectation mortality in the intensive-control group was higher as well as severe hypoglycemia. No difference though was observed in regards of length of stay in ICU, duration of hospitalization, days of mechanical ventilation, rate of pos. blood cultures and RBC transfusion. This month Kalfon et al. add another puzzle piece to this ongoing discussion with an article published in Intensive Care Medicine. This multi-center randomized trial included 2648 patients who were randomly assigned to tight computerized (CDSS) glucose control or conventional glucose control. And guess what: tight glucose control did not change 90-day mortality but was associated with more frequent severe hypoglycemia... In summary: there is not much in favor for tight glucose control coming up and there’s no need to invest in more expensive computers... Sweet! Kalfon P. et al. Intensive Care Med. 2014 Jan 14 van den Berghe, G. et al. Intensive insulin therapy in critically ill patients. N. Engl. J. Med. 345, 1359–1367 (2001) NICE-SUGAR study investigators. Intensive versus conventional glucose control in critically ill patients. N. Engl. J. Med. 360, 1283–1297 (2009) Wiener, R. S., Wiener, D. C. & Larson, R. J. Benefits and risks of tight glucose control in critically ill adults: a meta-analysis. JAMA 300, 933–944 (2008) Intensivists have repeatedly been warning on the potential effect side effects when infusing bigger quantities of normal saline like acidosis and potentially worse outcomes. It is well recognized that infusion of normal saline can lead to metabolic acidosis, but the link between the acidity of saline solution and the acidaemia it can produce might be not straightforward! This article from the beginning of this year shows a surprising insight on the various components involved when using normal saline infusions and comes to the conclusion that the acidaemia complicating saline infusions is actually unrelated to the acidity of the normal saline solution itself. It turns out that in vitro the acidity of a normal saline solution is mainly due to dissolved CO2 and PVC degradation of the bag containing the solution. The metabolic acidosis by saline infusions in vivo though mainly results from from buffer base dilution and is not directly related to the pH of the infusion at all. Got interested? Reddi B, et al. Int J Med Sci. 2013 Apr;10(6):747-50 Back in 2011 a primary analysis of the EPaNIC trial was published in the New Engalnd Journal of Medicine and showed that delaying total parenteral nutrition (TPN) for one week in critically ill patients resulted in better outcomes from a range of measures includung risk of infection and earlier release. The role of weakness remained unclear. This time Hermans et al. published a prospectively planned subanalysis of this trial, where weakness was assessed in 600 ICU patients out of which 122 patients had muscle biopsies performed to study for autophagy and atrophy. They were able to show that early TPN resulted in a significant greater number of patients with weakness compared to late TPN (not before day eight after admission to ICU). Weakness also recovered faster with late TPN. Interestingly autophagy marker were higher in patients given late TPN and this was independently associated with less weakness. Dr. Van den Bergen says:"The late PN strategy, that is, not using artificial (parenteral but maybe also forcing enteral) feeding during the acute phase of critical illness, should be standard of care, as there is absolutely no good data to support benefit from such forceful feeding and there is, as we have shown, risk for harm."... and I get the feeling he might be right. Hermanns G. et al. The Lancet Respiratory Medicine, 10 September 2013; volume 1, issue 8 Casaer MP et al. N Engl J Med. 2011 Aug 11;365(6):506-17 In this randomized, non-inferiority multi-center trial in 5 swiss teaching hospitals, 314 patients that presented to casualty with exacerbation of COPD were enrolled. They were treated with oral prednisolon for either 5 or 14 days.
Results showed that a 5-day treatment was non-inferior to a 14-day treatment with regard to re-exacerbation within 6 months but significantly reduced glucocorticoid exposure. As so often: Less is more! Leuppi JD, et al. JAMA. 2013 Jun 5;309(21):2223-31 50% of all pregnant women suffer of sometimes severe nausea and vomitus, especially at the beginning of their pregnancy. In a cohort of 600’000 pregnancies, in which 25% of all women took Ondansetron, no increased risk for fetal abnormalities or miscarriages was shown. A good news for all pregnant, though the risk of QT prolongation has to be considered.
Paternak B, et al. New Engl J Med. 2013;368:814-23 Dopamine has been widely used in the past for improving renal function but was abandoned due to lack of evidence and various potential serious side effects. In the new Heart Failure Guidelines 2013 of the AHA.pdf there is an interesting note in the section hospitalized patients with heart failure: low-dose dopamine infusion may be considered in addition to loop diuretic therapy to improve diuresis and better improve renal function. The level of evidence is IIb/B which means that efficacy is less well established and that there is greater conflicting evidence from trials. Indeed, when looking at the cited articles more questions than answer remain... but see yourself.
Giamouzis G, et al. .J Card Fail. 2010 Dec;16(12):922-30 Elkayam U, et al. Circulation. 2008 Jan 15;117(2):200-205 |
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