29 Sep 07
Ten years of vasopressin research in septic shock: Constant dripping wears the stone
By A Morelli, C Ertmer, M Westphal
Crit Care Med 2007;35:2447-2448
Arginine vasopressin belongs to the oldest substances in the pharmacologic armament of critical care physicians. The effects of purified pituitary extract on blood pressure were first recognized in the early 20th century. Although vasopressin and its analogs have emerged as standard drugs in the treatment of central diabetes insipidus and gastroesophageal hemorrhage, there is still no consensus on the use of vasopressin analogs in counteracting arterial hypotension. In cases of severe upper gastrointestinal bleeding, physicians often do not hesitate to administer several milligrams of terlipressin to terminate hemorrhage. Conversely, we are still very cautious with low-dose vasopressin infusion in septic shock patients, especially when such a concept yields to supraphysiologic plasma levels. And we are right to do so because several studies revealed severe complications after vasopressin administration in shock states. In this context, it is of note that most of these unwanted side effects are dose dependent. For example, van Haren et al. reported a proportional increase in the gastric mucosal Pco2 gap of septic shock patients in response to increased vasopressin plasma levels. On the contrary, several other clinical studies did not notice a negative effect of vasopressin therapy on organ function or outcome. Landry et al. even suggested relative vasopressin deficiency as a key factor in the pathogenesis of vasodilatory shock. In addition, the same authors noticed a pressor hypersensitivity in response to infusion of low vasopressin doses without obvious side effects.
Just recently, the results of the Vasopressin and Septic Shock Trial (unpublished) were presented at several major critical care meetings. These data provide evidence for the safety of a low-dose arginine vasopressin infusion (≤0.03 units/min), though the investigators did not observe an overall reduction in mortality. However, the results of an a priori analysis showed an improved survival rate of patients allocated to the vasopressin group in the less severe state of the disease (i.e., baseline norepinephrine dosage of <15 μg/min).