[Clinical effects of naloxone on hemorrhagic shock]. Naloxone fails to reverse blood pressure in shock: a double blind study in man. Naloxone and methylprednisolone sodium succinate enhance sympathomedullary discharge in patients with septic shock. Prospective, controlled, randomized trial of naloxone infusion in early hyperdynamic septic shock. Effects of prolonged naloxone infusion in septic shock.
In order to study the clinical effects of naloxone on hemorrhagic shock, 21 patients with moderate hemorrhagic shock were randomly divided into two groups. The naloxone group (NLX group) was infused normal saline (200ml) and naloxone (0.02mg/kg) via central vein while the control group was infused normal saline (200ml) only. Mean arterial pressure (MAP), central vein pressure (CVP), cardiac output (CO), cardiac index (CI), peripheral vascular resistance (PVR), levels of lactic acid in both artery and vein, and levels of catecholamine in artery were measured before and after the administration of naloxone or normal saline. The results showed that naloxone significantly increased blood level of catecholamine and MAP (P < 0.01), the effects sustained for more than 15 minutes with an increased PVR (P < 0.05). After infustion of normal saline, blood level of lactic acid in artery and vein decreased slightly (P > 0.05), yet comparatively lower in artery. On the contrary, after administration of naloxone, the blood level of lactic acid markedly decreased in both artery and vein (P < 0.01), but higher in artery. It is suggested that naloxone improve tissue oxygen supply temporarily with enhancement of tissue lactic acid metabolism. nan Naloxone and methylprednisolone sodium succinate (MPSS) may act in synergy to improve hemodynamics in patients with septic shock by enhancement of sympathomedullary discharge. This randomized double-blind study describes the effect of various dosing regimens of naloxone and MPSS upon hemodynamics and plasma catecholamines in patients with septic shock (n = 57). Consecutive bolus doses of naloxone were given 30 minutes apart (10 micrograms/kg;-100 micrograms/kg) and a single dose of MPSS (30 mg/kg); bolus doses of 5% dextrose in water solution plus single dose of MPSS as above; bolus dose of naloxone (30 micrograms/kg) followed by continuous infusion (30 micrograms/kg/hr for 1 hour) with single dose of MPSS as above; a bolus and continuous infusion of naloxone as above without MPSS; MPSS alone and standard therapy alone. In patients treated with bolus doses of naloxone in combination with MPSS, plasma levels of epinephrine and norepinephrine were increased approximately five-to tenfold. In patients treated with bolus plus continuous infusion of naloxone given with or without MPSS, only plasma epinephrine levels were increased. Systolic blood pressure and left ventricular stroke work index were improved within 15 minutes in groups which received naloxone and corticosteroids regardless of dose. In those groups, there were no changes in heart rate or filling pressure. Systemic vascular resistance improved significantly only in the group which received low dose bolus and continuous infusion of naloxone and MPSS. Naloxone and MPSS quickly improved cardiac function in patients with septic shock by enhanced sympathomedullary discharge and may be useful as an adjunct in the therapy of this disorder. To determine whether naloxone infusion is efficacious in severe hyperdynamic septic shock, we conducted a prospective study of 22 patients randomly assigned to a naloxone or placebo group. Patients were treated 12 +/- 2 h (SEM) after the onset of shock, with a mean arterial pressure (MAP) of 63 +/- 3 mm Hg. All patients had clinical evidence of an infectious process and required dopamine 20 +/- 2 micrograms/kg.min. Five (46%) of 11 patients in the naloxone group and one (9%) of the other 11 patients in the placebo group responded clinically. The MAP among the five responders increased from 62 +/- 5 to 89 +/- 4 mm Hg within 20 min of naloxone treatment (p less than .01). This favorable hemodynamic response was sustained throughout the patients' clinical course. In contrast, the MAP did not change significantly in the nonresponders who received naloxone, nor did it change in the placebo group. More patients in the naloxone group than in the placebo group received steroids concurrently. Survival rate was 100% in those who responded to naloxone clinically. However, overall survival rate in each group was essentially the same. No adverse effects were observed, except for mild agitation in some of the patients receiving naloxone. We conclude that naloxone infusion is clinically efficacious in improving the hemodynamic profile of a subgroup of patients with severe early hyperdynamic septic shock, but does not appear to improve the overall survival rate. Fourteen patients suffering sixteen episodes of septic shock requiring inotrope and/or vasopressor support were randomised to receive a 30 micrograms/kg naloxone intravenous bolus followed by a 30 micrograms/kg/h infusion or an equivalent volume placebo bolus and infusion for 8-16 h in a double-blind study. pH and pulmonary wedge pressure were kept constant, and inotrope and/or vasopressor were titrated to maintain a preselected mean blood pressure. Inotrope/vasopressor requirements in the naloxone-treated group were significantly lower than those in the control group at 8 h (eight patients in each group, p less than 0.005) and at 16 h (five patients in each group, p less than 0.02). Late but significant improvements in stroke volume (p less than 0.02) and heart rate (p less than 0.05) were also noted in the eight naloxone-treated patients.
Naloxone improves blood pressure, especially mean arterial blood pressure. However, the clinical usefulness of naloxone to treat shock remains to be determined and additional randomized controlled trials are needed to assess its usefulness.