Thursday, September 16, 2010

SICU Rounds Report - Sept 13th, 2010

Fixing da NAASTI with IVIG
IVIG is extracted and purified immunglobilin pooled from thousands of human donors. It's used in a variety of autoimmune and inflammatory conditions where the patients may benefit from one of two intended goals: 1) protect the recipient from infection or 2) to suppress immune-mediated or inflammatory disease processes. The first successful case report of its use was published in JAMA in 1992 and described its use in a previously healthy 32 year-old women with severe toxic shock syndrome who showed dramatic improvement after IVIG. A rash of case series in patients with group A strep infections followed which were almost always positive (the biggest series, 21 patients compared to historic controls, halved mortality rates 66 to 33%, P=0.02). Finally, a small RTC was published that showed a 3.6x reduction in mortality, though this did not reach statistical significance, probably because of its small size.  For other types of sepsis, it doesn't appear to help one bit.
There are many forms available, though they are all considered equivalently efficacious. Side effects are primarily phlogistic and may be minimized by concominant anti-histamine and/or steroids. Transmission of viral illness is a remote concern. Rare side effects include renal failure, bronchospasm and all the skin falling off.
Barry, W, Hudgins, L, Donta, S, Pesanti, E. Intravenous immunoglobulin therapy for toxic shock syndrome. JAMA 1992; 267:3315.
Kaul, R, McGeer, A, Norrby-Teglund, A, et al. Intravenous immunoglobulin therapy for streptococcal toxic shock syndrome — A comparative observational study. Clin Infect Dis 1999; 28:800.
Darenberg, J, Ihendyane, N, Sjolin, J, et al. Intravenous immunoglobulin G Therapy in streptococcal toxic shock syndrome: A European randomized, double-blind, placebo-controlled trial. Clin Infect Dis 2003; 37:333.

Therapeutic Hypercapnia. Positive pressure ventilation is bad for lungs. Over time, it has become clear that the bigger the tidal volume, the bigger the lung injury. (BTW, this appears to be true even at low tidal volumes). The definitive clinical proof of this concept came with the ARDSnet trial in JAMA (2000) that showed small (average 6 ml/kg) vs big (11 ml/kg) TV can reduced mortality in ARDS by 25%. However, ventilating with these small tidal volumes leads to elevated blood levels of carbon dioxide. This was tolerated to preserve the lung from volutrauma and call "permissive hypercapnia." Recently, animal data has suggested that hypercapnic acidosis created in these conditions might be beneficial per se (i.e. independent of the lung protective ventilation).  Previously, worsening acidosis was associated with worsening outcome, but this effect is not causal but associative. Looking back at the ARDSNet data using multivariate logistic regressional analysis while controlling for comorbidities and injury severity, researches found a benefit to hypercarbia in the high tidal volumes group.

How might it all work? Many pre-clinical trials have found that hypercapnic acidosis appears to attenuate ischemic-reperfusion injury in the heart, head and lungs. These trials have been done with the direct administration of CO2, suggesting the beneficial effects are from hypercapnia and not acidosis. The overall effect appears to be related to vascular tone and remodeling. For now, there is not enough data for recommendations to be made so sit tight and wait and see how it all flushes out. In the meantime, you can relax a bit when you ARDS patient has a PCO2 of 68.
The Acute Respiratory Distress Syndrome Network (2000) Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med 342:1301–1308
Kregenow DA, Rubenfeld G, Hudson L, Swenson ER (2003) Permissive hypercapnia reduces mortality with 12 ml/kg tidal volumes in acute lung injury. Am J Resp Crit Care Med 167:A616

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