Low-dose Vasopressin Infusion Research Articles

Low-Dose vasopressin and renal perfusion in pediatric cardiac surgery.

Congenital heart surgeries are associated with post-bypass renal and cardiac dysfunctions. The use of low-dose vasopressin has been found to be beneficial in adult cardiac surgeries. To assess the hemodynamic and renal effects of patients undergoing on-pump pediatric cardiac surgery under general anesthesia (GA) with low-dose vasopressin infusion. Prospective randomized controlled study. Operation room and ICU, tertiary care teaching hospital. Fifty-five pediatric cardiac patients undergoing repair for congenital heart diseases (CHD). Low-dose vasopressin infusion in the study group and placebo in the control group. Renal near-infrared spectroscopy (NIRS), serum NGAL, and inflammatory mediators-IL6 and IL8 along with other renal and hemodynamic parameters in the perioperative period were recorded. Diastolic blood pressure (DBP) and cardiac index were significantly higher in the vasopressin group. Inflammatory markers were significantly high in the immediate postoperative period in all patients which later stabilized in the next 48 h but showed similar trends in both groups. Low-dose vasopressin infusion did not improve either renal perfusion or function. The duration of mechanical ventilation and length of hospital stay, the incidence of AKI development, and transfusion requirements were marginally lower in the vasopressin group, although not significant. Low-dose vasopressin infusion improved hemodynamics and showed a decreased incidence of complications. However, it failed to show any benefit of renal function and overall outcome in pediatric cardiac surgery.

OTHR-36. Management of Central Diabetes Insipidus (CDI) with Low-Dose Vasopressin Infusion in Patients with Non-Germinomatous Germ Cell Tumors (NGGCT) Requiring Hyperhydration during Chemotherapy

Primary intracranial germ cell tumors (GCT) represent 3-5% of central nervous system tumors with non-germinomatous germ cell tumors (NGGCTs) comprising approximately one-third. Located in the pineal and suprasellar regions, the tumors can cause central diabetes insipidus (CDI). Induction chemotherapy for NGGCT includes ifosfamide. Due to the risk of hemorrhagic cystitis associated with ifosfamide, 3000 mL/m2/day of intravenous fluids is administered. Oral desmopressin (DDAVP), the mainstay of treatment for CDI, has a long duration of action, variable intensity and can lead to hyponatremia and water intoxication due to the retention of large quantities of free water. Therefore, DDAVP is held during hyperhydration resulting in significant diuresis leading to patient discomfort and increased risk for wide electrolyte fluctuations. The volume of dextrose-containing IV fluids also places patients at risk for hyperglycemia and other metabolic disturbances. Patients with NGGCTs and CDI at our institution are admitted to the ICU for ifosfamide cycles due to the need for close monitoring and prompt interventions. ICU admission can delay therapy and potentially places patients in a setting where staff are unfamiliar with chemotherapy administration, increasing the risk of safety-related events. From a cost, resource, and patient care perspective, these admissions are suboptimal. This prompted a search for evidence to maintain patients safely out of the ICU. A literature search provided case studies citing the use of low-dose IV vasopressin. In collaboration with our endocrine and pharmacy colleagues we created a protocol to treat patients with CDI receiving chemotherapy with hyperhydration with a low-dose, easily titratable intravenous vasopressin infusion, to keep urine mildly diluted to allow enough diuresis to decrease injury while preventing excessive fluid losses and wide variations in electrolytes.

Successful treatment of severe chronic hyponatremia complicated by bacterial pneumonia with continuous infusion of low-dose vasopressin: A case report

Successful treatment of severe chronic hyponatremia complicated by bacterial pneumonia with continuous infusion of low-dose vasopressin: A case report

A brief review of the use of vasopressin in critically ill children

Robust clinical evidence for the use of vasopressin in children is scant. Low dose vasopressin infusions may be tried in catecholamine resistant shock or refractory cardiac arrest. It significantly improves hemodynamic indices without necessarily translating into clinical benefit. There appears to be a trend to greater tissue ischemia with its use. Evidence to date has not demonstrated clear efficacy for vasopressin’s routine use in management of pediatric shock. Further high-quality research is essential before it can be recommended as a routine standard of care.

Low-Dose Vasopressin Improves Cardiac Function in Newborn Piglets With Acute Hypoxia-Reoxygenation

Cardiovascular dysfunction in asphyxiated neonates contributes significantly to their morbidity and mortality. We have recently shown that a low-dose vasopressin infusion (0.005 - 0.01 units/kg per hour) may improve myocardial oxygen transport balance in a swine model of neonatal hypoxia-reoxygenation. We aimed to compare the systemic and regional hemodynamic effects of low-dose vasopressin to dobutamine, a synthetic beta-adrenoreceptor agonist. Piglets (1 - 5 days old, 1.6 - 2.2 kg) were anesthetized and instrumented to continuously monitor systemic hemodynamic parameters, including cardiac output and mesenteric flow indices. After 2 h of hypoxia (10% - 15% O2), piglets had normoxic reoxygenation for 4 h. In a blinded randomized fashion, piglets received infusion of either vasopressin (0.01 units/kg per hour started at 30 min of reoxygenation) or dobutamine (20 μg/kg per minute started at 2 h of reoxygenation) (n = 8 per group). Hypoxia-reoxygenation controls (placebo, n = 8) and sham-operated (n = 5) piglets were also studied. Tissue lactate, glutathione, glutathione disulfide, and lipid hydroperoxides levels and histology of the left ventricle and the small bowel were analyzed. Plasma was also analyzed for troponin-I and intestinal fatty acid-binding protein levels. Piglets subjected to hypoxia-reoxygenation had cardiogenic shock and metabolic acidosis, which improved on reoxygenation. During recovery, cardiac output and mesenteric flows gradually deteriorated and were increased similarly in vasopressin- and dobutamine-treated piglets (P < 0.05 vs. controls). Plasma troponin-I and left ventricular lactate levels were lower in the vasopressin and dobutamine groups (P < 0.05 vs. controls), with no difference in the histological analysis among groups. The intestinal GSSG/GSH ratio and lipid hydroperoxides level were lower in the vasopressin and dobutamine groups (P < 0.05 vs. controls). This study is the first to demonstrate that a low-dose vasopressin infusion used in the setting of neonatal swine model of hypoxia-reoxygenation is associated with an improvement in cardiac output and mesenteric perfusion.

Vasopressin reduces the cumulative epinephrine dose in hypothermic swine with traumatic brain injury

Prevention of secondary neurologic injuries is paramount for improved neurologic outcomes after traumatic brain injury (TBI). Evidence suggests that although therapeutic hypothermia (TH) lowers intracranial pressure and attenuates secondary cerebral insults after TBI [1], it also induces hypotension. Brief episodes of mild hypotension in brain-injured patients can trigger secondary injuries, which have been associated with increased mortality in patients with TBI [2]. Vasopressin mitigates hypotension in septic shock and improves coronary perfusion in hypothermic cardiac arrest models [3]. We hypothesized that a low-dose vasopressin infusion may reduce the cumulative epinephrine dose in hypothermic, brain-injured swine.

Infusion of low-dose vasopressin improves left ventricular function during separation from cardiopulmonary bypass: A double-blind randomized study

We aimed to investigate whether low-dose vasopressin administered to patients undergoing coronary artery bypass grafting (CABG) surgery with preexisting mild to moderate systolic dysfunction can produce sustained improvement in cardiac function. This double-blind randomized study was conducted in a hospital where a single anesthetic and surgical team performed elective CABG. Twenty patients aged 32-61 years who underwent elective CABG between January 2007 and December 2007 were enrolled in this study. The patients randomly received either vasopressin 0.03 IU/min (Group A) or normal saline (Group B) in equal volume for 60 min after cardiopulmonary bypass (CPB). The cardiac output, cardiac index, stroke volume index, fractional area of contraction and systemic vascular resistance index were significantly higher in Group A than in Group B. Adrenaline (mean dose: 0.06 μg/kg x min-1) was required in seven patients from Group B but in none of the Group A patients on initial separation from CPB (P< 0.05). Of the 10 patients in Group B, five required phenylepherine to maintain the mean arterial pressure (MAP) >65 mmHg, whereas none of the Group A patients required phenylephrine for MAP regulation (P< 0.05). We conclude that Infusion of low-dose vasopressin for patients with mild to moderate left ventricular systolic dysfunction during separation from CPB is beneficial for the postoperative hemodynamic profile, reduces the catecholamine doses required and improves left ventricular systolic function.

Impact of Low‐dose Vasopressin on Trauma Outcome: Prospective Randomized Study

We previously found that regardless of the animal injury model used resuscitation strategies that minimize fluid administration requirements lead to better outcomes. We hypothesized that a resuscitation regimen that limited the total volume of fluid administered would reduce morbidity and mortality rates in critically ill trauma patients. We performed a double-blind randomized trial to assess the safety and efficacy of adding vasopressin to resuscitative fluid. Subjects were hypotensive adults who had sustained acute traumatic injury. Subjects were given fluid alone (control group) or fluid plus vasopressin (experimental group), first as a bolus (4 IU) and then as an intravenous infusion of 200 ml/h (vasopressin 2.4 IU/h) for 5 h. We randomly assigned 78 patients to the experimental group (n=38) or the control group (n=40). The groups were similar in age, sex, preexisting medical illnesses, and mechanism and severity of injury. Serum vasopressin concentrations were higher in the experimental group than in the control group at admission, after infusion of vasopressin (p=0.01), and 12 h later. The experimental group required a significantly lower total volume of resuscitation fluid over 5 days than did the control group (p=0.04). The mortality rate at 5 days was 13% in the experimental group and 25% in the control group (p=0.19). The rates of adverse events, organ dysfunction, and 30-day mortality were similar. This is the first trial to investigate the impact of vasopressin administration in trauma patients. Infusion of low-dose vasopressin maintained elevated serum vasopressin levels and decreased fluid requirements after injury.

Low‐dose vasopressin infusion therapy for refractory hypotension in ELBW infants

Severe hypotension in infants, especially in preterm infants, is associated with poor neurological outcome and high mortality. In adults, low-dose vasopressin (arginine vasopressin: AVP) infusion therapy has been effective for treating hypotension that is refractory to vasopressors and inotropes. The effects of AVP infusion therapy for refractory hypotension were retrospectively evaluated in extremely low-birthweight infants. Between January 2002 and November 2005, 22 infants with refractory hypotension treated with low-dose AVP infusion were reviewed. The average birthweight was 658 g (+/-142 g), and the average gestational age was 24.9 weeks (+/-1.4). The changes in blood pressure, urinary output, and other parameters in response to AVP therapy were analyzed in all the infants. After AVP infusion, systolic blood pressure increased from 30 mmHg to 43 mmHg (P < 0.0001), and the diastolic pressure increased from 15 mmHg to 24 mmHg (P < 0.0001). The urine output dramatically increased from 1.5 mL/kg per h to 4.0 mL/kg per h (P < 0.0001). AVP infusion, however, was not effective in four of the 22 patients (18%). The sodium concentration in the serum decreased mildly after administration. In six patients the serum sodium concentration decreased below 130 mEq/L. Severe mitral regurgitation was observed in two patients. Three infants showed a transient decrease in the platelet count during AVP infusion. Low-dose AVP therapy should be considered as rescue therapy when high-dose catecholamine therapy and/or steroid administration do not produce sufficient increase in the blood pressure. Further investigations are required to prove the efficacy and safety of AVP infusion therapy in preterm infants.

Perioperative infusion of low- dose of vasopressin for prevention and management of vasodilatory vasoplegic syndrome in patients undergoing coronary artery bypass grafting-A double-blind randomized study

Preoperative medication by inhibitors of angiotensin-converting enzyme (ACE) in coronary artery patients predisposes to vasoplegic shock early after coronary artery bypass grafting. Although in the majority of the cases this shock is mild, in some of them it appears as a situation, "intractable" to high-catecholamine dose medication. In this study we examined the possible role of prophylactic infusion of low-dose vasopressin, during and for the four hours post-bypass after cardiopulmonary bypass, in an effort to prevent this syndrome. In addition, we studied the influence of infused vasopressin on the hemodynamics of the patients, as well as on the postoperative urine-output and blood-loss. In our study 50 patients undergoing coronary artery bypass grafting were included in a blind-randomized basis. Two main criteria were used for the eligibility of patients for coronary artery bypass grafting: ejection fraction between 30-40%, and patients receiving ACE inhibitors, at least for four weeks preoperatively. The patients were randomly divided in two groups, the group A who were infused with 0.03 IU/min vasopressin and the group B who were infused with normal saline intraoperativelly and for the 4 postoperative hours. Measurements of mean artery pressure (MAP), central venous pressure (CVP), systemic vascular resistance (SVR), ejection fracture (EF), heart rate (HR), mean pulmonary artery pressure (MPAP), cardiac index (CI) and pulmonary vascular resistance (PVR) were performed before, during, and after the operation. The requirements of catecholamine support, the urine-output, the blood-loss, and the requirements in blood, plasma and platelets for the first 24 hours were included in the data collected. The incidence of vasodilatory shock was significantly lower (8% vs 20%) in group A and B respectively (p = 0,042). Generally, the mortality was 12%, exclusively deriving from group B. Postoperatively, significant higher values of MAP, CVP, SVR and EF were recorded in the patients of group A, compared to those of group B. In group A norepinephrine was necessary in fewer patients (p = 0.002) and with a lower mean dose (p = 0.0001), additive infusion of epinephrine was needed in fewer patients (p = 0.001), while both were infused for a significant shorter infusion-period (p = 0.0001). Vasopressin administration (for group A) was associated with a higher 24 hour diuresis) (0.0001).In conclusion, low-dose of infused vasopressin during cardiopulmonary bypass and for the next 4 hours is beneficial for its postoperative hemodynamic profile, reduces the doses of requirements of catecholamines and contributes to prevention of the postcardiotomy vasoplegic shock in the patient with low ejection fraction who is receiving ACE preoperatively.

Effects of Vasoactive Agents on Blood Loss and Transfusion Requirements During Pre-Reperfusion Stages of the Orthotopic Liver Transplantation

Objective: To evaluate the effects of vasoactive drugs, specifi cally low-dose vasopressin and phenylephrine infusions, on blood loss / transfusion requirements during dissection and anhepatic (pre-reperfusion) stages of orthotopic liver transplantations. Methods: A retrospective analysis of 110 orthotopic liver transplantation (OLT) cases was performed. The variables studied were: blood loss before and after reperfusion of the liver graft; blood volumes returned by cell-saver and amounts of transfused blood products; amounts of infused colloids and crystalloids; hemodynamic parameters such as MABP, MPAP, CO/CI, SVR; dosage of vasoactive drugs. Short – and long-term outcome measures included length-of stay (LOS), ICU LOS, 48 –hours return to the OR rate, incidence of the primary non-function of the liver graft, amounts of fresh frozen plasma (FFP) and cryoprecipitate, administered in the ICU, and 1-year mortality. The study subjects were allocated in two groups. Study group consisted of 15 patients that received a low-dose (0.04U/min) vasopressin infusion alongside with other vasoactive agents, such as phenylephrine and epinephrine, during the dissection and anhepatic stages of the procedure. Control group consisted of 95 patients, that received the same vasoactive agents except a lowdose vasopressin infusion. Anesthetic and transfusion management in both groups were otherwise identical. Results: The estimated blood loss before reperfusion of the liver graft was in 50.2% lower (p=0.0094) and total blood loss was in 38.8% lower ( p=0.0548) in the vasopressin group in comparison with control group of subjects of the same age, sex and with the same MELD score. No statistically signifi cant differences neither in hemodynamic parameters between the two groups, nor in transfusion requirements and volumes of crystalloid and colloids infused, were detected. No differences were found also in long-term outcome parameters. Conclusions: The decrease in blood loss in the vasopressin group may be attributed to the use of a vasopressin infusion. A low-dose (0.04U/min) vasopressin infusion may be an effective technique for blood loss reduction during the pre-reperfusion stages in orthotopic liver transplantation.

Prophylactic Vasopressin in Patients Receiving the Angiotensin-Converting Enzyme Inhibitor Ramipril Undergoing Coronary Artery Bypass Graft Surgery

The purpose of this study was to compare the effects of continuation versus discontinuation of the angiotensin-converting enzyme (ACE) inhibitor ramipril and assess the efficacy of prophylactic vasopressin infusion on hemodynamic stability and vasoactive drug requirements in patients undergoing coronary artery bypass graft (CABG) surgery. A prospective, randomized, double-blinded, single-center clinical study. Tertiary care hospital. Forty-seven patients on the ACE inhibitor ramipril for 6 weeks before undergoing elective primary CABG surgery on cardiopulmonary bypass (CPB). Patients were randomly divided into 3 groups: group A (n = 16), patients discontinued ramipril 24 hours before surgery; group B (n = 16), patients continued ramipril until the morning of surgery; and group C (n = 15), patients continued ramipril until the morning of surgery and received vasopressin infusion (0.03 U/min) from the onset of rewarming until the hemodynamics were stable without vasopressor agents. The anesthetic technique and conduct of CPB were standardized for all the groups. Hemodynamic parameters and vasoactive drug requirements were recorded for 3 days postoperatively. Patients in group A maintained stable mean arterial pressure (MAP) and systemic vascular resistance (SVR). In group B, MAP and SVR decreased after the induction of anesthesia and remained so throughout surgery (p < 0.05). In group C, MAP and SVR decreased upon the induction of anesthesia (p < 0.05) but normalized after CPB. Preoperative ACE inhibitor continuation predisposed to hypotension upon the induction of anesthesia and in the post-CPB period. Prophylactic low-dose vasopressin infusion prevented post-CPB hypotension. Low-dose vasopressin can be considered as potential therapy in these patients.

The effects of vasopressin on acute kidney injury in septic shock

To compare the effects of vasopressin versus norepinephrine infusion on the outcome of kidney injury in septic shock. Post-hoc analysis of the multi-center double-blind randomized controlled trial of vasopressin versus norepinephrine in adult patients who had septic shock (VASST). Seven hundred seventy-eight patients were randomized to receive a blinded infusion of either low-dose vasopressin (0.01-0.03 U/min) or norepinephrine infusion (5-15 microg/min) in addition to open-label vasopressors and were included in the outcome analysis. All vasopressors were titrated and weaned to maintain a target blood pressure. RIFLE criteria for acute kidney injury were used to compare the effects of vasopressin versus norepinephrine. In view of multiple simultaneous comparisons, a p value of 0.01 was considered statistically significant. Kidney injury was present in 464 patients (59.6%) at study entry. In patients in the RIFLE "Risk" category (n = 106), vasopressin as compared with norepinephrine was associated with a trend to a lower rate of progression to renal "Failure" or "Loss" categories (20.8 vs. 39.6%, respectively, p = 0.03), and a lower rate of use of renal replacement therapy (17.0 vs. 37.7%, p = 0.02). Mortality rates in the "Risk" category patients treated with vasopressin compared to norepinephrine were 30.8 versus 54.7%, p = 0.01, but this did not reach significance in a multiple logistic regression analysis (OR = 0.33, 99% CI 0.10-1.09, p = 0.02). The interaction of treatment group and RIFLE category was significant in predicting mortality. Vasopressin may reduce progression to renal failure and mortality in patients at risk of kidney injury who have septic shock.

Pilot safety study of low-dose vasopressin in non-septic critically ill children

To assess the safety of low-dose vasopressin infusion in critically ill children requiring prolonged mechanical ventilation (MV) at risk of developing sedation/analgesia-related hypotension. Randomized pilot safety study in children expected to require MV for at least 3 days. Children received either vasopressin (0.0005 U/kg/min) or sodium chloride (0.9%) infusion for a period of 48 h. Haemodynamic variables, urine output and serum electrolytes were closely monitored and analyzed. Twelve children in each group had similar baseline characteristics. Vasopressin infusion was associated with an 8 mmol/L fall in serum sodium concentration (p < 0.01) and with higher incidence of hyponatraemia (8 vs. 66%, p < 0.01). In normotensive children, low-dose vasopressin also induced a reversible decrease in urine output, and acutely increased blood pressure (p < 0.01). After stopping the vasopressin there was rebound hypotension (p < 0.01). Low-dose vasopressin infusion in haemodynamically stable, but critically ill, children is associated with reduction in urine output and decreased serum sodium level, yielding a high incidence of hyponatraemia. We conclude that these effects limit further study of prophylactic vasopressin for sedation-related hypotension in a randomized controlled trial.

Bench-to-bedside review: Vasopressin in the management of septic shock

This review of vasopressin in septic shock differs from previous reviews by providing more information on the physiology and pathophysiology of vasopressin and vasopressin receptors, particularly because of recent interest in more specific AVPR1a agonists and new information from the Vasopressin and Septic Shock Trial (VASST), a randomized trial of vasopressin versus norepinephrine in septic shock. Relevant literature regarding vasopressin and other AVPR1a agonists was reviewed and synthesized. Vasopressin, a key stress hormone in response to hypotension, stimulates a family of receptors: AVPR1a, AVPR1b, AVPR2, oxytocin receptors and purinergic receptors. Rationales for use of vasopressin in septic shock are as follows: first, a deficiency of vasopressin in septic shock; second, low-dose vasopressin infusion improves blood pressure, decreases requirements for norepinephrine and improves renal function; and third, a recent randomized, controlled, concealed trial of vasopressin versus norepinephrine (VASST) suggests low-dose vasopressin may decrease mortality of less severe septic shock. Previous clinical studies of vasopressin in septic shock were small or not controlled. There was no difference in 28-day mortality between vasopressin-treated versus norepinephrine-treated patients (35% versus 39%, respectively) in VASST. There was potential benefit in the prospectively defined stratum of patients with less severe septic shock (5 to 14 μg/minute norepinephrine at randomization): vasopressin may have lowered mortality compared with norepinephrine (26% versus 36%, respectively, P = 0.04 within stratum). The result was robust: vasopressin also decreased mortality (compared with norepinephrine) if less severe septic shock was defined by the lowest quartile of arterial lactate or by use of one (versus more than one) vasopressor at baseline. Other investigators found greater hemodynamic effects of higher dose of vasopressin (0.06 units/minute) but also unique adverse effects (elevated liver enzymes and serum bilirubin). Use of higher dose vasopressin requires further evaluation of efficacy and safety. There are very few studies of interactions of therapies in critical care - or septic shock - and effects on mortality. Therefore, the interaction of vasopressin infusion, corticosteroid treatment and mortality of septic shock was evaluated in VASST. Low-dose vasopressin infusion plus corticosteroids significantly decreased 28-day mortality compared with corticosteroids plus norepinephrine (44% versus 35%, respectively, P = 0.03; P = 0.008 interaction statistic). Prospective randomized controlled trials would be necessary to confirm this interesting interaction. In conclusion, low-dose vasopressin may be effective in patients who have less severe septic shock already receiving norepinephrine (such as patients with modest norepinephrine infusion (5 to 15 μg/minute) or low serum lactate levels). The interaction of vasopressin infusion and corticosteroid treatment in septic shock requires further study.

Low-dose vasopressin infusion results in increased mortality and cardiac dysfunction following ischemia-reperfusion injury in mice

IntroductionArginine vasopressin is a vasoactive drug commonly used in distributive shock states including mixed shock with a cardiac component. However, the direct effect of arginine vasopressin on the function of the ischemia/reperfusion injured heart has not been clearly elucidated.MethodsWe measured left ventricular ejection fraction using trans-thoracic echocardiography in C57B6 mice, both in normal controls and following ischemia/reperfusion injury induced by a one hour ligation of the left anterior descending coronary artery. Mice were treated with one of normal saline, dobutamine (8.33 μg/kg/min), or arginine vasopressin (0.00057 Units/kg/min, equivalent to 0.04 Units/min in a 70 kg human) delivered by an intraperitoneal micro-osmotic pump. Arterial blood pressure was measured using a micromanometer catheter. In addition, mortality was recorded and cardiac tissues processed for RNA and protein.ResultsBaseline left ventricular ejection fraction was 65.6% (60 to 72). In normal control mice, there was no difference in left ventricular ejection fraction according to infusion group. Following ischemia/reperfusion injury, AVP treatment significantly reduced day 1 left ventricular ejection fraction 46.2% (34.4 to 52.0), both in comparison with baseline and day 1 saline treated controls 56.9% (42.4 to 60.2). There were no significant differences in preload (left ventricular end diastolic volume), afterload (blood pressure) or heart rate to account for the effect of AVP on left ventricular ejection fraction. The seven-day mortality rate was highest in the arginine vasopressin group. Following ischemia/reperfusion injury, we found no change in cardiac V1 Receptor expression but a 40% decrease in Oxytocin Receptor expression.ConclusionsArginine vasopressin infusion significantly depressed the myocardial function in an ischemia/reperfusion model and increased mortality in comparison with both saline and dobutamine treated animals. The use of vasopressin may be contraindicated in non-vasodilatory shock states associated with significant cardiac injury.

Vasopressin in septic shock: pressing questions remain

Background: The use of low-dose vasopressin as an adjunctive vasopressor in septic shock is common, but its effect on mortality is unknown. Objective: To determine whether a low-dose vasopressin infusion reduces mortality in septic shock when added to an infusion of norepinephrine. Design and Setting: Multicentre, multiple-blinded, randomized controlled trial conducted in three countries from July, 2001 to April, 2006. Patients: Inclusion criteria were patients C17 years of age with septic shock requiring C5 ug min of norepinephrine (or equivalent) for C6 h, or requiring C15 ug min of norepinephrine (or equivalent) for C3 h, despite having received C500 ml of normal saline. Study enrolment was only permitted within 24 h of meeting inclusion criteria. Exclusion criteria included previous use of vasopressin, acute myocardial infarction, New York Heart Association class III or IV congestive heart failure, acute mesenteric ischemia, severe traumatic brain injury, hyponatremia \130 mmol l, Raynaud’s phenomenon, systemic sclerosis, vasospastic diathesis, pregnancy, an irreversible condition with an estimated six-month mortality C50%, anticipated death within 12 hr, or the decision not to proceed with aggressive care. Intervention: Study patients were randomized to a blinded infusion of vasopressin (started at 0.01 U min and titrated to 0.03 U min over 40 min) or norepinephrine (started at 5 ug min and titrated to 15 ug min over 40 min). Additional open-label vasopressors (excluding vasopressin) were administered as necessary to maintain a target mean arterial pressure (MAP) of 65–75 mmHg. The study drug could be tapered after the target MAP had been maintained for[8 h without open-label vasopressors. Measurements: The primary outcome was 28-day mortality. Secondary outcomes included 90-day mortality, rates of adverse events, and markers of clinical illness (e.g., organ dysfunction scores, need for vasopressors, mechanical ventilation, and renal replacement therapy). A priori subgroup analysis was performed on patients with less severe vs more severe septic shock (defined by the need for 5–14 ug min vs. C15 ug min of norepinephrine, respectively, at the time of study enrolment). Main results: Seven hundred seventy-eight patients were included in the final analysis. There were no statistically significant differences between the vasopressin and the norepinephrine groups in terms of 28-day mortality (35.4 vs. 39.3%, respectively, P = 0.26), 90-day mortality (43.9 vs. 49.6%, respectively, P = 0.11), rates of organ dysfunction, or overall rates of adverse events. Patients with less severe septic shock who were randomized to vasopressin had a trend towards decreased 28-day mortality (26.5 vs. 35.7%, respectively, P = 0.05) and 90-day mortality (35.8 vs. 46.1%, respectively, P = 0.04). Conclusions: An adjunctive vasopressin infusion does not reduce overall mortality in septic shock, but may benefit patients with less severe septic shock. R. Keyes, MD (&) P. G. Brindley, MD University of Alberta, Edmonton, Canada e-mail: rkeyes@ualberta.ca

Current place of vasopressin analogues in the treatment of septic shock

Arginine vasopressin and terlipressin increase mean arterial pressure and reduce catecholamine requirements in septic shock patients. Infusing either agent may reduce incidence of new-onset tachyarrhythmias and improve renal function. The recent Vasopressin and Septic Shock Trial did not demonstrate an overall survival benefit of arginine vasopressin infusion (0.03 U/min) compared with norepinephrine (15 microg/min). However, patients with less severe septic shock (ie, < 15 microg/min of norepinephrine) at arginine vasopressin initiation had a lower 28-day mortality rate compared with norepinephrine-only infusion (26.5% vs 35.7%; P = 0.05). An unpublished study comparing terlipressin (1.3 microg/kg/h), arginine vasopressin (0.03 U/min), and norepinephrine (15 microg/min) as first-line vasopressors showed that terlipressin had higher efficacy than arginine vasopressin in reducing catecholamine requirements. Current literature suggests that early infusion of low-dose continuous arginine vasopressin or terlipressin appears superior to a last-resort treatment. However, because no large clinical trials have proven terlipressin's safety in patients with septic shock, arginine vasopressin is preferred until more data are available.

Role of vasopressin in the treatment of anaphylactic shock in a child undergoing surgery for congenital heart disease: a case report

IntroductionThe incidence of anaphylactic reactions during anesthesia is between 1:5000 and 1:25000 and it is one of the few causes of mortality directly related to general anesthesia. The most important requirements in the treatment of this clinical condition are early diagnosis and maintenance of vital organ perfusion. Epinephrine administration is generally considered as the first line treatment of anaphylactic reactions. However, recently, new pharmacological approaches have been described in the treatment of different forms of vasoplegic shock.Case presentationWe describe the case of a child who was undergoing surgery for ventricular septal defect, with an anaphylactic reaction to heparin that was refractory to epinephrine infusion and was effectively treated by low dose vasopressin infusion.ConclusionIn case of anaphylactic shock, continuous infusion of low-dose vasopressin might be considered after inadequate response to epinephrine, fluid resuscitation and corticosteroid administration.

Vasopressin in vasodilatory and septic shock

The aim of this article is to review mechanisms of action of vasopressin and clinical studies of vasopressin in septic shock. Arginine vasopressin is an important stress hormone that has both vasoactive and antidiuretic properties. The vasoactive properties of vasopressin have been more applicable clinically because of the discovery by Landry and colleagues that there is a deficiency of vasopressin in septic shock and that infusion of relatively low doses of vasopressin improves responsiveness to infused catecholamines (such as norepinephrine). There are at least 16 clinical studies of infusion of vasopressin in patients who have septic shock. The majority of studies found that vasopressin infusion increased blood pressure and urine output, and decreased the dose requirement of norepinephrine. Several studies showed that vasopressin infusion increased urine output. Both vasopressin and norepinephrine have important adverse effects including decreased cardiac output, decreased heart rate, arrhythmias, myocardial ischemia, mesenteric ischemia, and digital ischemia. It is still unclear whether there is net benefit from low dose vasopressin infusion in patients who have septic shock. There may be certain patients who benefit but there are few studies of a prolonged vasopressin infusion to determine which patients benefit.