ICU Literature
Alice in Intensiveland (Chest 1995;108(4):1129)
My 14 bets (not in a specific order), from 1998 ’til now: 1. Finfer S, Bellomo R, Boyce N, French J, Myburgh J, Norton R; SAFE Study Investigators. A comparison of albumin and saline for fluid resuscitation in the intensive care unit. N Engl J Med. 2004 May 27;350(22):2247-56. 4% albumin is as safe as saline, albumin is bad in trauma and may be useful in sepsis, colloid to cristalloid is not 1 to 3 2. Hebert PC, Wells G, Blajchman MA, Marshall J, Martin C, Pagliarello G, Tweeddale M, Schweitzer I, Yetisir E. A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. Transfusion Requirements in Critical Care Investigators, Canadian Critical Care Trials Group. N Engl J Med. 1999 Feb 11;340(6):409-17. No need to give RBCs, maybe the supranormal oxygen delivery trials failed bec of this? 3. Chastre J, Wolff M, Fagon JY, Chevret S, Thomas F, Wermert D, Clementi E, Gonzalez J, Jusserand D, Asfar P, Perrin D, Fieux F, Aubas S; PneumA Trial Group. Comparison of 8 vs 15 days of antibiotic therapy for ventilator-associated pneumonia in adults: a randomized trial. JAMA. 2003 Nov 19;290(19):2588-98. At last someone has shown it. There’s a M Kollef paper in Chest proposing an even better protocol. 4. Richard C, Warszawski J, Anguel N, Deye N, Combes A, Barnoud D, Boulain T, Lefort Y, Fartoukh M, Baud F, Boyer A, Brochard L, Teboul JL; French Pulmonary Artery Catheter Study Group. Early use of the pulmonary artery catheter and outcomes in patients with shock and acute respiratory distress syndrome: a randomized controlled trial. JAMA. 2003 Nov 26;290(20):2713-20. Here’s the population we’re really interested, the timing is correct and the result is… 5. Lopez A, Lorente JA, Steingrub J, Bakker J, McLuckie A, Willatts S, Brockway M, Anzueto A, Holzapfel L, Breen D, Silverman MS, Takala J, Donaldson J, Arneson C, Grove G, Grossman S, Grover R. Multiple-center, randomized, placebo-controlled, double-blind study of the nitric oxide synthase inhibitor 546C88: effect on survival in patients with septic shock. Crit Care Med. 2004 Jan;32(1):21-30. Not everything that shines is gold, not every drug that makes the BP higher is better. 6. Esteban A, Frutos-Vivar F, Ferguson ND, Arabi Y, Apezteguia C, Gonzalez M, Epstein SK, Hill NS, Nava S, Soares MA, D’Empaire G, Alia I, Anzueto A. Noninvasive positive-pressure ventilation for respiratory failure after extubation. N Engl J Med. 2004 Jun 10;350(24):2452-60. NIV is for patients in a very narrow window, after they failed extubation is too late. 7. Esteban A, Anzueto A, Frutos F, Alia I, Brochard L, Stewart TE, Benito S, Epstein SK, Apezteguia C, Nightingale P, Arroliga AC, Tobin MJ; Mechanical Ventilation International Study Group. Characteristics and outcomes in adult patients receiving mechanical ventilation: a 28-day international study. JAMA. 2002 Jan 16;287(3):345-55. Tell me, why SIMV was still the most widely MV mode used in this planet? 8. Hebert PC, Yetisir E, Martin C, Blajchman MA, Wells G, Marshall J, Tweeddale M, Pagliarello G, Schweitzer I; Transfusion Requirements in Critical Care Investigators for the Canadian Critical Care Trials Group. Is a low transfusion threshold safe in critically ill patients with cardiovascular diseases? Crit Care Med. 2001 Feb;29(2):227-34. Complement to #2 9. Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, Knoblich B, Peterson E, Tomlanovich M; Early Goal-Directed Therapy Collaborative Group. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001 Nov 8;345(19):1368-77. Not an ICU trial, but with huge impacts on care. 10. Bellomo R, Chapman M, Finfer S, Hickling K, Myburgh J. Low-dose dopamine in patients with early renal dysfunction: a placebo-controlled randomised trial. Australian and New Zealand Intensive Care Society (ANZICS) Clinical Trials Group. Lancet. 2000 Dec 23-30;356(9248):2139-43. It’s useless for the kidney, it’s worse than norepinephrine, so it’s time restrict it to old textbooks 11. Gattinoni L, Tognoni G, Pesenti A, Taccone P, Mascheroni D, Labarta V, Malacrida R, Di Giulio P, Fumagalli R, Pelosi P, Brazzi L, Latini R; Prone-Supine Study Group. Effect of prone positioning on the survival of patients with acute respiratory failure. N Engl J Med. 2001 Aug 23;345(8):568-73. After the hype, the real thing. It’s not bad, it may be useful in a very limited group of patients. 12. Amato MB, Barbas CS, Medeiros DM, Magaldi RB, Schettino GP, Lorenzi-Filho G, Kairalla RA, Deheinzelin D, Munoz C, Oliveira R, Takagaki TY, Carvalho CR. Effect of a protective-ventilation strategy on mortality in the acute respiratory distress syndrome. N Engl J Med. 1998 Feb 5;338(6):347-54. That why we do not use prone position so often. This old paper has still the best idea on how to ventilate ARDS 13. van den Berghe G, Wouters P, Weekers F, Verwaest C, Bruyninckx F, Schetz M, Vlasselaers D, Ferdinande P, Lauwers P, Bouillon R. Intensive insulin therapy in the critically ill patients. N Engl J Med. 2001 Nov 8;345(19):1359-67. She (GVDB) came from almost nothing, like Einstein’s theories, to change ICU practices. 14. Annane D, Sebille V, Charpentier C, Bollaert PE, Francois B, Korach JM, Capellier G, Cohen Y, Azoulay E, Troche G, Chaumet-Riffaut P, Bellissant E. Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA. 2002 Aug 21;288(7):862-71. I would like to sell hydrocortisone and insulin [ ]s, Fred from.br — Michael Kuiper <mi.kuiper@wxs.nl> a écrit : > I would suggest to include the CRASH trial in the Top Ten > of recently > published papers. (Final results of MRC CRASH, a randomised > > placebo-controlled trial of intravenous corticosteroid in > adults with head > injury-outcomes at 6 months.Lancet. 2005;365:1957-9) This > study shows that > steroids, while effective in many diseases, are certainly > not a good thing > in head injury. > > Michael
1. The SAFE study 4% albumin is as safe as saline, albumin is bad in trauma and may be useful in sepsis, colloid to cristalloid is not 1 to 3 Albumin and saline are equally SAFE. (Can’t resist). Subgroup analyses are underpowered and not significant and may be confounded by severity. Trauma subgroup is being examined for this issue by the SAFE investigators but similar enquiry for sepsis group is not planned. Pity. Note that ratio of volume of fluids is only given for study as a whole (what is this ratio in the sepsis group?) and that the haemodynamic data suggested that the two groups were not resuscitated to equivalent blood volumes (saline group a little less) but that IT DID NOT MATTER. 2. TRICC study No need to give RBCs, maybe the supranormal oxygen delivery trials failed bec of this? This trial is unhappily lacking in external validity because of the enormous number of patients eligible but not randomised. In fact 2039 patients were eligible but in 598 there was “physician refusal” and in another 603 “patient or family refusal” so that only 838 (41%) of eligible patients were randomised. Let me suggest that “physician refusal” may have tapped into some “high-risk” features that were not part of the exclusion criteria. The authors allude to this in the dicussion when they say “A greater proportion of patients with severe cardiac disease than with other types of disease had attending physicians who declined to enroll them in our study”. Interestingly, Manny Rivers paper showed that 3. Shorter course for VAP. JAMA. 2003 Nov 19;290(19):2588-98. At last someone has shown it. There’s a M Kollef paper in Chest proposing an even better protocol. I’m with you on this one Fred. 4. French Pulmonary Artery Catheter Study Group. JAMA. 2003 Nov 26;290(20):2713-20. Here’s the population we’re really interested, the timing is correct and the result is… Build a bridge guys and get over it. Throw it away. Stop believing in the cult. Stand at the bedside and just treat the patient intelligently. 5. L-NMMA study. Crit Care Med. 2004 Jan;32(1):21-30. Not everything that shines is gold, not every drug that makes the BP higher is better. Agreed. However, it was a pity (=”major study fault” IMAO) that one was allowed to randomise patients with low-flow. Who would give a major vascular clamp to someone with cold icy edges, anuria and ischaemic hepatitis. It just doesn’t make sense. What about the subgroup with high-flow ? What I want to know is — those patients with high flow and no pressure — are they better off with this or vasopressin or high-dose noradrenaline or even steroids (which modify i-NOS and raise BP in sespsis by reducing endotoxin-induced NO by i-NOS). 6. NIV after extubation. N Engl J Med. 2004 Jun 10;350(24):2452-60. NIV is for patients in a very narrow window, after they failed extubation is too late. Yeah, I agree. However NIV for some docs is turning into a convenient “hammer” — everything looks like a nail. 7. Characteristics and outcomes in adult patients receiving mechanical ventilation: a 28-day international study. JAMA. 2002 Jan 16;287(3):345-55. Tell me, why SIMV was still the most widely MV mode used in this planet? I don’t know ! It sure ain’t in NZ. 8. TRICC #2. Crit Care Med. 2001 Feb;29(2):227-34. Complement to #2 Same problems too — external validity. Note the “nonsignifiant” increase in mortality is those with “severe IHD”. Interpret with caution. 9. Rivers E et al. N Engl J Med. 2001 Nov 8;345(19):1368-77. Not an ICU trial, but with huge impacts on care. Yes, but is it a marketing tool for Edwards or an illustration of the time-critical nature of aggressive treatment for the disease we call “sepsis”. If you think (as I do) that sepsis patients should be out of the ED in similar time frames to trauma patients (i.e. under one hour) then this surely is an “ICU trial”. Get out of the ICU and get these patients quickly ! 10. ANZICS Dopamine trial. Lancet. 2000 Dec 23-30;356(9248):2139-43. It’s useless for the kidney, it’s worse than norepinephrine, so it’s time restrict it to old textbooks It does not reduce the need for dialysis (etc). However, it still has some useful haemodynamic properties (like chronotropy without much effect on vascular resistance at modest doses) which mean that it might have a place in treatment of shock, or in patients with cerebral artery vasospasm or pre-treated with beta-blockers. Don’t use it for “magical powers” but don’t throw it out of the cupboard. There is more to life than renal failure. 11. Effect of prone positioning on the survival of patients with acute respiratory failure. N Engl J Med. 2001 Aug 23;345(8):568-73. After the hype, the real thing. It’s not bad, it may be useful in a very limited group of patients. Very difficult study to do. The trial “fizzled out” into an underpowered state because of a developing lack of equipoise in the study participants. Pity. I guess we use prone because it “helps oxygenation” in some patients and because it “facilitates drainage” in some patients. No magical properties on “survival” in this underpowered trial (with very high mortality in both groups …) 12. Amato MB et al. N Engl J Med. 1998 Feb 5;338(6):347-54. That why we do not use prone position so often. This old paper has still the best idea on how to ventilate ARDS. Hmmm. For those of us using pressure-controlled ventilation and permissive hypercapnia for the last 40 years (!) this was not too surprising. However, it seemed like the “control group” were being ventilated with a strategy which was “way too big” and neither group was really representative of what goes on in NZ (and Australia). 13. van den Berghe G. N Engl J Med. 2001 Nov 8;345(19):1359-67. She (GVDB) came from almost nothing, like Einstein’s theories, to change ICU practices. I agree — a pervasive cult has developed after only one RCT. Lets hear about the morbidity and mortality of intensive therapy “outside of study conditions” — some recent British data are alarming. Meanwhile — we are recruiting fast into NICE (Normoglycaemia in Intensive Care Evaluation) — another sterling effort by the ANZICS CTG, in collaboration with the Canadian CCTG. We have randomised around 60 patients in our department so far. Study size (>5000 patients, perhaps 7000 if the Canadians are firmly “on-side” — enlighten me someone from the CTG), “general ICU population” and a similar “deferred consent” process to SAFE will help to answer the “external validity” and “power” questions that persist after GVDB’s study. 14. Annane D et al. JAMA. 2002 Aug 21;288(7):862-71. I would like to sell hydrocortisone and insulin. I’m less convinced. Underpowered trial. Overly “optimistic” assumptions in power analyses (e.g. 95% mortality in “non-responders” placebo group). One-sided testing — “not interested in whether steroids might increase mortality”. (Remember CRASH?). Two interim analyses (at 114 and 220 patients only). No significant difference in mortality in “all patients” (n=299). Only significant difference in “non-responders” (failure to increase cortisol concentration by 9 micrograms per decilitre after ACTH. Now what about “CRASH” — was it the death of “killeroids” in trauma ? S, from NZ. Stephen Streat FRACP
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