Impact of bolus application of low-dose hydrocortisone on glycemic control in septic shock patients

Objective To determine whether glycemic control is less feasible when hydrocortisone is given as a bolus compared with continuous application in septic shock patients. Design Observational prospective pilot study. Setting Fourteen-bed surgical university hospital ICU. Patients Sixteen consecutive patients with septic shock receiving a continuous infusion of 200 mg hydrocortisone/day and an infusion regime of insulin keeping blood glucose below 150 mg/dl. Intervention Blood glucose and insulin infusion were adjusted to steady state before intervention. At baseline, the continuous hydrocortisone infusion was replaced with a single bolus of 50 mg hydrocortisone. During a subsequent 6-h period, blood glucose was monitored hourly and insulin infusion was kept constant. Afterwards, hydrocortisone application and adjustment of blood glucose was resumed according to standard treatment. Results Mean blood glucose in steady state at baseline immediately prior to intervention was 128 mg/dl (range 114–141 mg/dl; 95% confidence interval). After bolus injection of hydrocortisone, blood glucose increased significantly within 6 h with peak levels of 154 mg/dl (range 132–178 mg/dl; p < 0.01). Blood glucose returned to baseline with restoration of continuous hydrocortisone infusion. There were marked inter-individual variations with peak glucose values up to 254 mg/dl, but no significant difference in intra-individual glucose variability before and after bolus injection of hydrocortisone. Conclusions Bolus injections of hydrocortisone may induce significant increases of blood glucose in patients with septic shock. The individual response is highly variable and we speculate that repetitive boluses would induce marked undulation of blood glucose. In terms of glycemic-control strategies, a continuous infusion of hydrocortisone seems to be preferable.     

Hypertonic fluid administration in patients with septic shock: a prospective randomized controlled pilot study

We assessed the short-term effects of hypertonic fluid versus isotonic fluid administration in patients with septic shock. This was a double-blind, prospective randomized controlled trial in a 15-bed intensive care unit. Twenty-four patients with septic shock were randomized to receive 250 mL 7.2% NaCl/6% hydroxyethyl starch (HT group) or 500 mL 6% hydroxyethyl starch (IT group). Hemodynamic measurements included mean arterial blood pressure (MAP), central venous pressure, stroke volume index, stroke volume variation, intrathoracic blood volume index, gastric tonometry, and sublingual microcirculatory flow as assessed by sidestream dark field imaging. Systolic tissue Doppler imaging velocities of the medial mitral annulus were measured using echocardiography to assess left ventricular contractility. Log transformation of the ratio MAP divided by the norepinephrine infusion rate (log MAP/NE) quantified the combined effect on both parameters. Compared with the IT group, hypertonic solution treatment resulted in an improvement in log MAP/NE (P = 0.008), as well as an increase in systolic tissue Doppler imaging velocities (P = 0.03) and stroke volume index (P = 0.017). No differences between the groups were found for preload parameters (central venous pressure, stroke volume variation, intrathoracic blood volume index) or for afterload parameters (systemic vascular resistance index, MAP). Hypertonic solution treatment decreased the need for ongoing fluid resuscitation (P = 0.046). No differences between groups were observed regarding tonometry or the sublingual microvascular variables. In patients with septic shock, hypertonic fluid administration did not promote gastrointestinal mucosal perfusion or sublingual microcirculatory blood flow in comparison to isotonic fluid. Independent of changes in preload or afterload, hypertonic fluid administration improved the cardiac contractility and vascular tone compared with isotonic fluid. The need for ongoing fluid resuscitation was also reduced.     

Dyslipidemia: a prospective controlled randomized trial of intensive glycemic control in sepsis

Purpose  

Metabolic disturbances are quite common in critically ill patients. Glycemic control appears to be an important adjuvant therapy in such patients. In addition, disorders of lipid metabolism are associated with worse prognoses. The purpose of this study was to investigate the effects that two different glycemic control protocols have on lipid profile and metabolism.     

Treatment of gram-negative septic shock with an immunoglobulin preparation: a prospective, randomized clinical trial

OBJECTIVE: To evaluate the effectiveness of a polyclonal immunoglobulin (Ig) preparation containing IgG, IgM, and IgA as an adjunctive therapy for septic shock. DESIGN: Prospective, randomized clinical trial. SETTING: A clinical immunology ward at the center for internal medicine in a university hospital. PATIENTS: Fifty-five patients with septic shock were randomly allocated to two groups according to criteria of septic shock. INTERVENTION: One group of patients (n = 27) received a commercially available immunoglobulin preparation (containing high titers of antibodies specific for determinants to bacterial endotoxin) during the first 3 days after inclusion in the study. The other randomized group (n = 28) did not receive any immunoglobulin preparation. MEASUREMENTS AND MAIN RESULTS: During the period of less than or equal to 6 wks after the beginning of clinically apparent septic shock, death related to the septic process occurred in one (4%) of 27 patients who received immunoglobulin. By comparison, nine (32%) of 28 control group patients died during this period (p less than .01). Within the first 48 hrs after onset of the clinically apparent septic process, significantly increased activity of circulating endotoxin and simultaneously decreased specific IgG serum titers to lipid A were detected in the group of nonsurvivors. CONCLUSION: Administration of a polyclonal immunoglobulin preparation in the early phase of septic shock was associated with significantly improved survival.     

小剂量氢化可的松在脓毒性休克治疗中的应用

目的 探讨小剂量氢化可的松对脓毒性休克患者炎性反应的疗效.方法 将脓毒性休克患者80例均予常规治疗.40例只行常规治疗(对照组);另40例加用小剂量氢化可的松治疗(氢可组).治疗后4、12、24、48 h、7 d采用ELISA法测定血浆TNF-α, IL-1β, IL-6和IL-10含量;治疗前及后24、48 h、7 d行急性生理功能和慢性健康状况(APACHEⅡ)评分,并检测降钙素原(PCT)以及皮质醇浓度,记录28 d病死率.结果 治疗前两组患者外周血上述指标水平差异无统计学意义.治疗前后比较, TNF-α、IL-1β和IL-6明显下降(P<0.05),IL-10差异无统计学意义;治疗24、48 h、7 d后APACHEⅡ评分下降(P<0.05)与对照组相比,在各时间点TNF-α,IL-1β,IL-6下降差异有统计学意义(P<0.05);APACHEⅡ评分降低(P<0.05),PCT下降(P<0.05),28 d病死率下降.但血皮质醇浓度与28 d生存率无明显相关性.结论 小剂量氢化可的松能减轻脓毒性休克患者的炎症反应,改善预后.     

Early initiation of low-dose hydrocortisone treatment for septic shock in adults: A randomized clinical trial

Background

Physiologic dose hydrocortisone is part of the suggested adjuvant therapies for patients with septic shock. However, the association between the corticosteroid therapy and mortality in patients with septic shock is still not clear. Some authors considered that the mortality is related to the time frame between development of septic shock and start of low dose hydrocortisone. Thus we designed a placebo-controlled, randomized clinical trial to assess the importance of early initiation of low dose hydrocortisone for the final outcome.

Comparing hydrocortisone and methylprednisolone in patients with septic shock

Introduction  Intravenous hydrocortisone of 200–300 mg/day for 7 days is suggested for patients with septic shock who require vasopressors to maintain mean artery pressure ≥65 mmHg, despite adequate fluid resuscitation. No study to date has compared the effects between physiologic doses of hydrocortisone and methylprednisolone in patients with septic shock. Methods  From July 2007 to June 2008, patients who were admitted to the intensive care unit at Chang Gung Memorial Hospital, Keelung, Taiwan, with low-dose steroid therapy due to septic shock were enrolled in this study. The typical steroid therapy included 7 days of intravenous hydrocortisone 50 mg every 6 hours. Methylprednisolone (20 mg every 12 hours) was replaced in these patients from January 2008 because no hydrocortisone could be prescribed. Results  A total of 21 patients were prescribed hydrocortisone and 19 patients were prescribed methylprednisolone. The survival rates for patients receiving hydrocortisone were relatively higher compared with those receiving methylprednisolone, but the difference was not significant. There were no significant differences in the Kaplan-Meier curves for the time to reverse shock between patients who received hydrocortisone, or methylprednisolone. Further regression analysis showed no significant independent factors associated with the survival rates and the time to reverse shock among age, sex, Acute Physiology and Chronic Health Evaluation II (APACHE II) score, histories, and adverse events. Conclusions  Low-dose methylprednisolone and hydrocortisone might have a similar effect for the treatment of patients with septic shock.     

Stress doses of hydrocortisone reverse hyperdynamic septic shock: a prospective, randomized, double-blind, single-center study.

OBJECTIVE: To investigate the effects of stress doses of hydrocortisone on the duration of vasopressor therapy in human septic shock. DESIGN: Prospective, randomized, double-blind, single-center study. SETTING: Twenty-bed multidisciplinary intensive care unit in a 1400-bed university hospital. PATIENTS: Forty consecutive patients who met the ACCP/SCCM criteria for septic shock. An additional criterion for inclusion in the study was vasopressor support and high-output circulatory failure with a cardiac index of >4 L/min/m2 after fluid resuscitation (pulmonary capillary wedge pressure: 12-15 mm Hg) and without the use of positive inotropes such as dobutamine or dopexamine. The primary study end point was the time to cessation of vasopressor support (norepinephrine or epinephrine in any dose, dopamine > or = 6 microg/kg/min). Secondary study end points were the evolution of hemodynamics and the multiple organ dysfunction syndrome (MODS). The severity of illness at recruitment was graded using the Acute Physiology and Chronic Health Evaluation II and the Simplified Acute Physiology Score II scoring systems. MODS was described by the Sepsis-related Organ Failure Assessment score. INTERVENTIONS: All eligible patients were prospectively randomized to receive either stress doses of hydrocortisone or placebo. Hydrocortisone was started with a loading dose of 100 mg given within 30 mins and followed by a continuous infusion of 0.18 mg/ kg/hr. When septic shock had been reversed, the dose of hydrocortisone was reduced to 0.08 mg/kg/hr. This dose was kept constant for 6 days. As soon as the underlying infection had been treated successfully or sodium serum concentrations had increased to >155 mmol/L, the hydrocortisone infusion was tapered in steps of 24 mg/day. Physiologic saline solution was the placebo. MEASUREMENTS AND MAIN RESULTS: Hemodynamic and oxygen-derived variables were measured at previously defined time points over a study period of 5 days. Relevant clinical and laboratory measurements were registered for a study period of 14 days to assess the evolution of organ dysfunction. Baseline data at recruitment did not differ between the two groups. Shock reversal was achieved in 18 of the 20 patients treated with hydrocortisone vs. 16 of the 20 patients treated with placebo. Hydrocortisone significantly reduced the time to cessation of vasopressor support. The median time of vasopressor support was 2 days (1st and 3rd Quartiles, 1 and 6 days) in the hydrocortisone-treated group and 7 days (1st and 3rd Quartiles, 3 and 19 days) in the placebo group (p = .005 Breslow test). There was a trend to earlier resolution of the organ dysfunction syndrome in the hydrocortisone group. CONCLUSIONS: Infusion of stress doses of hydrocortisone reduced the time to cessation of vasopressor therapy in human septic shock. This was associated with a trend to earlier resolution of sepsis-induced organ dysfunctions. Overall shock reversal and mortality were not significantly different between the groups in this low-sized single-center study.     

氢化可的松在肺部感染致感染性休克中应用的前瞻性临床研究

目的探讨早期小剂量氢化可的松对肺部感染致感染性休克患者病死率的影响。 方法采用前瞻性随机对照临床研究（RCT）方法,连续选择2015年9月至2017年2月收住于江苏省苏北人民医院重症监护病房（ICU）的54例肺部感染致感染性休克患者。将患者随机分为氢化可的松组和对照组。两组患者一旦使用血管活性药物,立即同时予以研究药物（氢化可的松或0.9%氯化钠溶液）持续静脉泵入。记录患者28 d病死率、住院病死率、休克逆转率、住ICU及住院时间等,评估早期小剂量氢化可的松的使用对肺部感染致感染性休克患者预后的影响。 结果两组患者在28 d病死率、住院病死率、休克逆转率、住ICU时间及住院时间等方面差异均无统计学意义（均P>0.05）。二分类Logistic回归模型分析显示28 d内机械通气时间是肺部感染致感染性休克患者28 d病死率的独立影响因素（OR=0.654,95%CI：0.498~0.860,P=0.002）。而小剂量氢化可的松的应用在Logistic回归模型分析中差异无统计学意义（P>0.05）。 结论在肺部感染致感染性休克患者中早期应用小剂量氢化可的松,并不能降低病死率、住ICU时间及住院时间。     

Fluconazole improves survival in septic shock: a randomized double-blind prospective study

OBJECTIVE: To demonstrate whether fluconazole reduces multiple organ failure and mortality in early septic shock (<24 hrs). DESIGN: A prospective randomized double-blind study. SETTING: A medical and surgical adult intensive care unit in a tertiary referral center. PATIENTS: Values were obtained from 71 general adult intensive care unit patients. INTERVENTIONS: During a 2.5-yr period, December 1998-June 2001, 71 patients with septic shock attributed to either nosocomial pneumonia (n = 37) or intra-abdominal sepsis (n = 34) were admitted to our intensive care unit and met the criteria of early septic shock and were entered into this study. All patients were randomized by our clinical pharmacist to receive daily either 200 mg of fluconazole in isotonic saline (fluconazole group = 32) or isotonic saline alone (placebo group = 39) intravenously during the course of their septic shock. MEASUREMENTS AND MAIN RESULTS: All patients were closely monitored with pulmonary artery catheters and parameters to calculate daily organ dysfunction and Acute Physiology and Chronic Health Evaluation II scores. There was a highly significant increase in 30-day survival in the fluconazole-treated patients compared with the placebo patients (78% vs. 46%). However, fluconazole was found to be more effective in patients with septic shock attributed to intra-abdominal sepsis than to nosocomial pneumonia. Increased survival in the intra-abdominal sepsis clinical category was mirrored by a significantly lower number of organ failures in the treated group compared with the placebo group whereas the number of organ failures in the fluconazole group attributed to nosocomial pneumonia were not significantly increased compared with the control group. The septic shock state was considered in all cases to be attributed to bacterial and not to disseminated yeast infection with the exception of one patient in the control group who was admitted with candidemia. The mechanisms by which fluconazole exerts its protective effect against septic shock in patients is far from clear. However, fluconazole has been shown to enhance bactericidal activity of neutrophils and also to inhibit transmigration and adhesion of neutrophils in capillaries of distant organs. CONCLUSIONS: The development of organ failure and mortality in septic shock was significantly reduced by fluconazole given intravenously. The mechanism of action of fluconazole in reducing multiple organ dysfunction in this group of patients may be attributed to the ability of fluconazole to increase recruitment, improve bactericidal activity of neutrophils, and to contain microorganisms locally.     

Effect of rapid fluid administration on the prognosis of septic shock patients with isolated hyperlactatemia: A prospective multicenter observational study

BackgroundWe aimed to investigate the association between initial fluid resuscitation in septic shock patients with isolated hyperlactatemia and outcomes.MethodsThis multicenter prospective study was conducted using the data from the Korean Shock Society registry. Patients diagnosed with isolated hyperlactatemia between October 2015 and December 2018 were included and divided into those who received 30 mL/kg of fluid within 3 or 6 h and those who did not receive. The primary outcome was in-hospital mortality; the secondary outcomes were intensive care unit (ICU) admission, length of ICU stay, mechanical ventilation, and renal replacement therapy (RRT).ResultsA total of 608 patients were included in our analysis. The administration of 30 mL/kg crystalloid within 3 or 6 h was not significantly associated with in-hospital mortality in multivariable logistic regression analysis ([OR, 0.8; 95% CI, 0.52–1.23, p = 0.31], [OR, 0.96; 95% CI, 0.59–1.57, p = 0.88], respectively). The administration of 30 mL/kg crystalloid within 3-h was not significantly associated with mechanical ventilation and RRT ([OR, 1.19; 95% CI, 0.77–1.84, p = 0.44], [OR, 1.2; 95% CI, 0.7–2.04, p = 0.5], respectively). However, the administration of 30 mL/kg crystalloid within 6 h was associated with higher ICU admission and RRT ([OR, 1.57; 95% CI, 1.07–2.28, p = 0.02], [OR, 2.08; 95% CI, 1.19–3.66, p = 0.01], respectively).ConclusionsInitial fluid resuscitation of 30 mL/kg within 3 or 6 h was neither associated with an increased or decreased in-hospital mortality in septic shock patients with isolated hyperlactatemia.     

Terlipressin or norepinephrine in hyperdynamic septic shock: a prospective, randomized study

OBJECTIVE: To compare, in patients with hyperdynamic septic shock, the effects of norepinephrine or terlipressin on hemodynamic variables and renal function. DESIGN: Prospective, randomized, open-label study. SETTING: Intensive care unit of a university, tertiary, and referral center. PATIENTS: Twenty adult patients with hyperdynamic septic shock, after fluid resuscitation. INTERVENTIONS: Patients were randomized to receive norepinephrine or terlipressin. Global hemodynamic variables, oxygen consumption, urine flow, creatinine clearance, and arterial blood lactate levels were measured. MEASUREMENTS AND MAIN RESULTS: Mean arterial pressure, systemic vascular resistance, pulmonary vascular resistance, and left and right ventricular stroke work were significantly increased with both drugs. With terlipressin, but not with norepinephrine, a significant decrease in heart rate (from 113 +/- 17 to 104 +/- 11 beats.min(-1), p < .01) and cardiac index (from 5.1 +/- 1.7 to 4.2 +/- 1.6 L.min(-1).m(-2)) was observed, with no change in stroke volume. Oxygen delivery index (from 784 +/- 131 to 701 +/- 92 mL.min(-1).m(-2)) and consumption index (from 244 +/- 69 to 210 +/- 54 mL.min(-1).m(-2)) were significantly decreased with terlipressin, but not with norepinephrine. Blood lactate concentrations were significantly decreased with both drugs. Urine flow and creatinine clearance were increased with both drugs. CONCLUSIONS: In patients with hyperdynamic septic shock, both norepinephrine and terlipressin were effective to raise mean arterial blood pressure. With terlipressin, but not norepinephrine, the improvement in blood pressure was achieved at the expense of cardiac index and oxygen consumption, which were significantly decreased. Renal function was improved with both drugs. In further studies, alternative strategies to maintain cardiac index should be explored, such as a synergy between low-dose terlipressin and dobutamine.     

Phenylephrine versus norepinephrine for initial hemodynamic support of patients with septic shock: a randomized, controlled trial

Introduction

Previous findings suggest that a delayed administration of phenylephrine replacing norepinephrine in septic shock patients causes a more pronounced hepatosplanchnic vasoconstriction as compared with norepinephrine. Nevertheless, a direct comparison between the two study drugs has not yet been performed. The aim of the present study was, therefore, to investigate the effects of a first-line therapy with either phenylephrine or norepinephrine on systemic and regional hemodynamics in patients with septic shock.

Methods

We performed a prospective, randomized, controlled trial in a multidisciplinary intensive care unit in a university hospital. We enrolled septic shock patients (n = 32) with a mean arterial pressure below 65 mmHg despite adequate volume resuscitation. Patients were randomly allocated to treatment with either norepinephrine or phenylephrine infusion (n = 16 each) titrated to achieve a mean arterial pressure between 65 and 75 mmHg. Data from right heart catheterization, a thermodye dilution catheter, gastric tonometry, acid-base homeostasis, as well as creatinine clearance and cardiac troponin were obtained at baseline and after 12 hours. Differences within and between groups were analyzed using a two-way analysis of variance for repeated measurements with group and time as factors. Time-independent variables were compared with one-way analysis of variance.

Results

No differences were found in any of the investigated parameters.

Conclusions

The present study suggests there are no differences in terms of cardiopulmonary performance, global oxygen transport, and regional hemodynamics when phenylephrine was administered instead of norepinephrine in the initial hemodynamic support of septic shock.

Trial registration

ClinicalTrial.gov NCT00639015     

Effect of computer-generated tailored feedback on glycemic control in people with diabetes in the community: a randomized controlled trial

OBJECTIVE

It is unknown whether computer-generated, patient-tailored feedback leads to improvements in glycemic control in people with type 2 diabetes.

RESEARCH DESIGN AND METHODS

We recruited people with type 2 diabetes aged ≥40 years with a glycated hemoglobin (A1C) ≥7%, living in Hamilton, Canada, who were enrolled in a community-based program (Diabetes Hamilton) that provided regular evidence-based information and listings of community resources designed to facilitate diabetes self-management. After completing a questionnaire, participants were randomly allocated to either receive or not receive periodic computer-generated, evidence-based feedback on the basis of their questionnaire responses and designed to facilitate improved glycemic control and diabetes self-management. The primary outcome was a change in A1C after 1 year.

RESULTS

A total of 465 participants (50% women, mean age 62 years, and mean A1C 7.83%) were randomly assigned, and 12-month A1C values were available in 96% of all participants, at which time the A1C level had decreased by an absolute amount of 0.24 and 0.15% in the intervention and control groups, respectively. The difference in A1C reduction for the intervention versus control group was 0.09% (95% CI −0.08 to 0.26; P = 0.3). No between-group differences in measures of quality of life, diabetes self-management behaviors, or clinical outcomes were observed.

CONCLUSIONS

Providing computer-generated tailored feedback to registrants of a generic, community-based program that supports diabetes self-management does not lead to lower A1C levels or a better quality of life than participation in the community-based program (augmented by periodic A1C testing) alone.Diabetes is a common chronic disease characterized by hyperglycemia that currently is estimated to affect >285 million people worldwide (1). People with diabetes are at high risk for serious chronic consequences, including retinopathy, nephropathy, blindness, cataracts, renal failure, limb amputation, cardiovascular events, and premature death. Indeed, the high prevalence and associated comorbidities cost $174 billion in the U.S. in 2007 alone (2,3). More than 90% of affected people have type 2 diabetes, and several large trials have shown that glucose-lowering strategies targeting an A1C <7% can reduce some of these health consequences (4,5). As such, most clinical practice guidelines recommend A1C measurement every 3 months with target values <7% (6,7).Evidence that self-management education can reduce the impact of diabetes (8–11) has led to recommendations that it be implemented for all individuals with diabetes (6,7). Information and resources designed to facilitate diabetes self-management have been freely available to people with diabetes residing in the region of Hamilton, Canada, since 1999 through a free community-based program (Diabetes Hamilton). After completing a brief questionnaire focused on diabetes-related health status and behaviors, registrants (and their primary care physicians) received access to an inventory of community resources, tools to facilitate self-care, and quarterly newsletters describing evidence-based information pertaining to diabetes. As of April 2010, >4,300 individuals (~10% of the city’s population with diabetes) have registered in the program and are being followed annually.A growing body of evidence pertaining to smoking cessation, blood pressure control, and lifestyle changes suggests that the provision of tailored information that is specific to a particular individual may achieve better health outcomes than generic information alone (12–17). Whether adding such feedback improves glycemic control and quality of life in people with diabetes in the community setting is unknown and was assessed in a randomized controlled trial.     

IgMA-enriched immunoglobulin in neutropenic patients with sepsis syndrome and septic shock: a randomized, controlled, multiple-center trial

OBJECTIVE: To evaluate the effect of intravenous IgMA-enriched immunoglobulin (ivIGMA) therapy on mortality in neutropenic patients with hematologic malignancies and sepsis syndrome or septic shock. DESIGN: Multiple-center, prospective randomized, controlled study. SETTING: Six university hospitals in Germany. PATIENTS: Patients were 211 neutropenic patients with sepsis syndrome or septic shock after chemotherapy for severe hematologic disorders between 1992 and 1999. INTERVENTIONS: Patients received 1300 mL of ivIGMA (7.8 g IgM, 7.8 g IgA, and 49.4 g IgG) infused intravenously within a period of 72 hrs or human albumin according to the same schedule as ivIGMA. MEASUREMENTS AND MAIN RESULTS: All-cause mortality at 28 days, sepsis-related mortality at 28 days, all-cause mortality at 60 days, mortality from septic shock, and mortality from microbiologically proven Gram-negative sepsis and septic shock were recorded. Immunoglobulin had no benefit over human albumin. The 28-day mortality rate was 26.2% and 28.2% in the ivIGMA and control patients, respectively (difference, 2.0% [95% confidence interval, -10.2 to 14.2 percentage points]). Likewise, the 60-day mortality rate did not differ between both arms (29.6% vs. 34.7% in the ivIGMA and control patients, respectively). Mortality rates in patients with sepsis syndrome (17.1% vs. 16.7%) and septic shock (51.9% vs. 54.8%) were also found to be similar between both groups. CONCLUSIONS: Intravenous ivIGMA had no beneficial effects in neutropenic patients with hematologic malignancies and sepsis syndrome and septic shock.     

Effect of hydrocortisone on phenylephrine--mean arterial pressure dose-response relationship in septic shock

BACKGROUND: Septic shock is characterized by decreased responsiveness to catecholamines. Because endogenous steroids are known to play a role in the modulation of vasomotor tone, the purpose of our study was to investigate the phenylephrine-mean arterial pressure dose-response relationship in patients with septic shock and the effect of a physiological dose of hydrocortisone on it. METHODS: Twelve patients meeting usual criteria for septic shock and 12 age-matched control subjects were investigated before and 1 hour after receiving 50 mg intravenous hydrocortisone. Sixteen incremental doses of phenylephrine (microg/kg/min) were infused, and the effects on mean arterial pressure (mm Hg) were recorded. A sigmoid model, E = E0 + [Emax x Dgamma/(ED50gamma + Dgamma)], was fitted to individual data. In this model, E is the predicted effect and D is the dose of phenylephrine infused. E0 represents the basal value of effect (ie, the value of mean arterial pressure without drug), Emax is the maximum theoretical effect, ED50 is the dose of phenylephrine for which an effect of 50% of Emax is observed, and gamma is the Hill coefficient which accounts for the sigmoidicity of the curve. RESULTS: As compared with in control subjects, in patients, E0 was decreased before (58 +/- 8 versus 73 +/- 7 mm Hg) and after (64 +/- 12 versus 82 +/- 10 mm Hg) administration of hydrocortisone (P = .0001 for group), Emax was reduced before (39 +/- 17 versus 84 +/- 18 mm Hg) and after (77 +/- 26 versus 106 +/- 21 mm Hg) administration of hydrocortisone (P = .0001 for group), ED50 was not modified, and gamma was increased before (3.5 +/- 1.8 versus 1.3 +/- 0.3) and after (1.9 +/- 1.1 versus 1.3 +/- 0.3) administration of hydrocortisone (P = .0010 for group). Hydrocortisone similarly increased E0 in both groups (P = .0003 for sequence, P = .2883 for interaction), increased more Emax in patients than in control subjects (P < .0001 for sequence; P = .0280 for interaction), did not change ED50, and decreased y in patients but not in control subjects (P = .0025 for sequence, P = .0025 for interaction). CONCLUSIONS: In patients with septic shock, the Emax of phenylephrine is decreased, whereas its ED50 is not modified, both before and after administration of hydrocortisone. A physiological dose of hydrocortisone tends to normalize the relationship.