Increasing mean arterial pressure in patients with septic shock: effects on oxygen variables and renal function

OBJECTIVE: To measure the effects of increasing mean arterial pressure on oxygen variables and renal function in septic shock. DESIGN: Prospective, open-label, randomized, controlled study. SETTING: Medical-surgical intensive care unit of a tertiary care teaching hospital. PATIENTS: Twenty-eight patients with a diagnosis of septic shock who required fluid resuscitation and pressor agents to increase and maintain mean arterial pressure > or =60 mm Hg. INTERVENTIONS: Patients were treated with fluid and norepinephrine to achieve and maintain a mean arterial pressure of 65 mm Hg. Then they were randomized in two groups: In the first group (control group, n = 14), mean arterial pressure was maintained at 65 mm Hg, and in the second group (n = 14), mean arterial pressure was increased to 85 mm Hg by increasing the dose of norepinephrine. MEASUREMENTS AND MAIN RESULTS: Hemodynamic variables (mean arterial pressure, heart rate, mean pulmonary artery pressure, pulmonary artery occlusion pressure, cardiac index, systemic vascular resistance index, pulmonary vascular resistance index, left and right ventricular stroke indexes), metabolic variables (oxygen delivery, oxygen consumption-calorimetric method, arterial lactate), and renal function variables (urine flow, serum creatinine, creatinine clearance) were measured. After introduction of norepinephrine, similar values of hemodynamic, metabolic, and renal function variables were obtained in both groups. No changes were observed in group 1 during the study period. Increasing mean arterial pressure from 65 to 85 mm Hg with norepinephrine in group 2 resulted in a significant increase in cardiac index from 4.8 (3.8-6.0) to 5.8 (4.3-6.9) L.min.m. Arterial lactate and oxygen consumption did not change. No changes were observed in renal function variables: urine flow, 63 (14-127) and 70 (15-121) mL; serum creatinine, 170 (117-333) and 153 (112-310) mumol.L; and creatinine clearance, 50 (12-77) and 67 (13-89) mL.min.1.73 m. CONCLUSIONS: Increasing mean arterial pressure from 65 to 85 mm Hg with norepinephrine neither affects metabolic variables nor improves renal function.     

Optimizing mean arterial pressure in septic shock: a critical reappraisal of the literature

Guidelines recommend that a mean arterial pressure (MAP) value greater than 65 mm Hg should be the initial blood pressure target in septic shock, but what evidence is there to support this statement? We searched Pubmed and Google Scholar by using the key words ‘arterial pressure’, ‘septic shock’, and ‘norepinephrine’ and retrieved human studies published between 1 January 2000 and 31 July 2014. We identified seven comparative studies: two randomized clinical trials and five observational studies. The results of the literature review suggest that a MAP target of 65 mm Hg is usually sufficient in patients with septic shock. However, a MAP of around 75 to 85 mm Hg may reduce the development of acute kidney injury in patients with chronic arterial hypertension. Because of the high prevalence of chronic arterial hypertension in patients who develop septic shock, this finding is of considerable importance. Future studies should assess interactions between time, fluid volumes administered, and doses of vasopressors.     

Increasing mean arterial blood pressure in sepsis: effects on fluid balance,vasopressor load and renal function

Introduction

The objective of this study was to evaluate the effects of two different mean arterial blood pressure (MAP) targets on needs for resuscitation, organ dysfunction, mitochondrial respiration and inflammatory response in a long-term model of fecal peritonitis.

Methods

Twenty-four anesthetized and mechanically ventilated pigs were randomly assigned (n = 8/group) to a septic control group (septic-CG) without resuscitation until death or one of two groups with resuscitation performed after 12 hours of untreated sepsis for 48 hours, targeting MAP 50-60 mmHg (low-MAP) or 75-85 mmHg (high-MAP).

Results

MAP at the end of resuscitation was 56 ± 13 mmHg (mean ± SD) and 76 ± 17 mmHg respectively, for low-MAP and high-MAP groups. One animal each in high- and low-MAP groups, and all animals in septic-CG died (median survival time: 21.8 hours, inter-quartile range: 16.3-27.5 hours). Norepinephrine was administered to all animals of the high-MAP group (0.38 (0.21-0.56) mcg/kg/min), and to three animals of the low-MAP group (0.00 (0.00-0.25) mcg/kg/min; P = 0.009). The high-MAP group had a more positive fluid balance (3.3 ± 1.0 mL/kg/h vs. 2.3 ± 0.7 mL/kg/h; P = 0.001). Inflammatory markers, skeletal muscle ATP content and hemodynamics other than MAP did not differ between low- and high-MAP groups. The incidence of acute kidney injury (AKI) after 12 hours of untreated sepsis was, respectively for low- and high-MAP groups, 50% (4/8) and 38% (3/8), and in the end of the study 57% (4/7) and 0% (P = 0.026). In septic-CG, maximal isolated skeletal muscle mitochondrial Complex I, State 3 respiration increased from 1357 ± 149 pmol/s/mg to 1822 ± 385 pmol/s/mg, (P = 0.020). In high- and low-MAP groups, permeabilized skeletal muscle fibers Complex IV-state 3 respiration increased during resuscitation (P = 0.003).

Conclusions

The MAP targets during resuscitation did not alter the inflammatory response, nor affected skeletal muscle ATP content and mitochondrial respiration. While targeting a lower MAP was associated with increased incidence of AKI, targeting a higher MAP resulted in increased net positive fluid balance and vasopressor load during resuscitation. The long-term effects of different MAP targets need to be evaluated in further studies.     

A high mean arterial pressure target is associated with improved microcirculation in septic shock patients with previous hypertension: a prospective open label study

IntroductionThe effect of mean arterial pressure titration to a higher level on microcirculation in septic shock patients with previous hypertension remains unknown. Our goal is to assess the effect of mean arterial pressure titration to a higher level on microcirculation in hypertensive septic shock patients.MethodsThis is a single-center, open-label study. Hypertensive patients with septic shock for less than 24 hours after adequate fluid resuscitation and requiring norepinephrine to maintain a mean arterial pressure of 65 mmHg were enrolled. Mean arterial pressure was then titrated by norepinephrine from 65 mmHg to the normal level of the patient. In addition to hemodynamic variables, sublingual microcirculation was evaluated by sidestream dark field imaging.ResultsNineteen patients were enrolled in the study. Increasing mean arterial pressure from 65 mmHg to normal levels was associated with increased central venous pressure (from 11 ± 4 to 13 ± 4 mmHg, P = 0.002), cardiac output (from 5.4 ± 1.4 to 6.4 ± 2.1 l/minute, P = 0.001), and central venous oxygen saturation (from 81 ± 7 to 83 ± 7%, P = 0.001). There were significant increases in small perfused vessel density (from 10.96 ± 2.98 to 11.99 ± 2.55 vessels/mm², P = 0.009), proportion of small perfused vessels (from 85 ± 18 to 92 ± 14%, P = 0.002), and small microvascular flow index (from 2.45 ± 0.61 to 2.80 ± 0.68, P = 0.009) when compared with a mean arterial pressure of 65 mmHg.ConclusionsIncreasing mean arterial pressure from 65 mmHg to normal levels is associated with improved microcirculation in hypertensive septic shock patients.

Trial registration

Clinicaltrials.gov: {"type":"clinical-trial","attrs":{"text":"NCT01443494","term_id":"NCT01443494"}}NCT01443494; registered 28 September 2011.

Electronic supplementary material

The online version of this article (doi:10.1186/s13054-015-0866-0) contains supplementary material, which is available to authorized users.     

Renal arterial resistance in septic shock: effects of increasing mean arterial pressure with norepinephrine on the renal resistive index assessed with Doppler ultrasonography

Objective To determine the effects of increasing mean arterial pressure (MAP) on renal resistances assessed by Doppler ultrasonography in septic shock. Design and setting Prospective, single-center, nonrandomized, open-label trial in the surgical intensive care unit in a university teaching hospital. Patients and participants 11 patients with septic shock who required fluid resuscitation and norepinephrine to increase and maintain MAP at or above 65 mmHg. Interventions Norepinephrine was titrated in 11 patients in septic shock during three consecutive not randomized periods of 2 h to achieve a MAP at successively 65, 75, and 85 mmHg. Measurements and results At the end of each period hemodynamic parameters and renal function variables (urinary output, creatinine, clearance) were measured, and Doppler ultrasonography was performed on interlobar arteries to assess the renal resistive index. When increasing MAP from 65 to 75 mmHg, urinary output increased significantly from 76 ± 64 to 93 ± 68 ml/h and the resistive index significantly decreased from 0.75 ± 0.07 to 0.71 ± 0.06. No difference was found between 75 and 85 mmHg. Conclusions Doppler ultrasonography and resistive index measurements may help determine in each patient the optimal MAP for renal blood flow and may be a relevant end-point to titrate the hemodynamic treatment in septic shock.     

Changes in heart rate,mean arterial pressure,and oxygen saturation after open and closed endotracheal suctioning: A prospective observational study

Purpose

It is widely assumed that closed suction systems (CSSs), as compared with open suction systems (OSSs), better guarantee optimal oxygenation with less disturbance of physiologic parameters in mechanically ventilated intensive care patients. We, therefore, quantified changes in heart rate (HR), mean arterial pressure (MAP), and peripheral oxygen saturation (Spo₂) in patients undergoing endotracheal suctioning (ES) with CSS and OSS.

Materials and Methods

We performed a prospective observational study nested within a crossover trial in 4 intensive care units between January 2007 and February 2008. Per unit, 50 ES procedures were selected at random, and HR, MAP, and Spo₂ were measured before and after ES.

Results

In total, 197 complete ES procedures (103 OSS and 94 CSS) were monitored. Mean HR, MAP, and Spo₂ changed directly after ES and returned to baseline after 5 minutes. Changes in HR and MAP were comparable after using CSS and OSS, whereas in Spo₂, slightly better values were monitored 3 and 5 minutes after OSS, these differences being rather small (0.3%-0.7%) and clinically not relevant.

Conclusions

Changes in HR, MAP, and Spo₂ were comparable and mild during and after CSS and OSS. Both systems can be considered equally safe.     

Impairment of renal function using hyperoncotic colloids in a two hit model of shock: a prospective randomized study

Introduction  

One of the therapeutic essentials in severe sepsis and septic shock is an adequate fluid replacement to restore and maintain circulating plasma volume, improve organ perfusion and nutritive microcirculatory flow. The type of solution to be used as a fluid replacement remains under discussion. The aim of the study was to evaluate the effects of clinically used fluid replacement solutions on renal function and inflammatory response.     

Evaluation of the relationship between slow-waves of intracranial pressure,mean arterial pressure and brain tissue oxygen in TBI: a CENTER-TBI exploratory analysis

Journal of Clinical Monitoring and Computing - Brain tissue oxygen (PbtO2) monitoring in traumatic brain injury (TBI) has demonstrated strong associations with global outcome. Additionally, PbtO2...     

Pathophysiological aspects of hyperglycemia in children with meningococcal sepsis and septic shock: a prospective,observational cohort study

Introduction  

The objective of this study was to investigate the occurrence of hyperglycemia and insulin response in critically ill children with meningococcal disease in the intensive care unit of an academic children's hospital.     

Effect of bladder volume on measured intravesical pressure: a prospective cohort study

Introduction  

Correct bedside measurement of intra-abdominal pressure (IAP) is important. The bladder method is considered as the gold standard for indirect IAP measurement, but the instillation volumes reported in the literature vary substantially. The aim of this study was to evaluate the effect of instillation volume on intra-bladder pressure (IBP) as an estimation for IAP in critically ill patients.     

Assessment of dynamic changes in cardiac function during resuscitation of patients with suspected septic shock: A prospective,observational, cohort study

Study objectiveTo describe changes in cardiac function throughout the course of resuscitation of patients with suspected septic shock.MethodsProspective observational cohort study of Point-of-Care Transthoracic Echocardiograms (TTE) obtained in Emergency Department (ED) patients with a presumed infectious cause of hypotension within one hour of initiating IV fluid resuscitation. Findings of this pre-resuscitation TTE were compared to mid-resuscitation TTE (obtained upon disposition from the ED), and post-resuscitation TTE (obtained after admission to hospital).Results22 enrolled patients had a second TTE available for comparison to the initial, pre-resuscitation TTE. 12 patients had a mid-resuscitation TTE and 16 patients had a post-resuscitation TTE. We observed a high incidence of changes on TTE during the clinical course of resuscitation (14/22 [64%]). Patients who developed LV or RV dysfunction during resuscitation were more likely to require vasopressor infusion and ICU admission (Spearman's coefficients [95% CI] of 0.68 [0.36–0.86] and 0.47 [0.04;0.75] respectively). Development of RV dysfunction alone was associated with increased use of positive pressure ventilation and vasopressor infusion (Spearman's coefficients [95% CI] of 0.43 [0;0.72] and 0.47 [0.05,0.75] respectively).ConclusionsCardiac function changes assessed by TTE are common during the resuscitation of patients with septic shock. These changes likely reflect the underlying physiology of patients with septic shock and correlate with need for interventions and higher level of care. Further work is required to characterize these changes and to elucidate how to use these physiologic data to guide management.     

Time-courses of lung function and respiratory muscle pressure generating capacity after spinal cord injury: a prospective cohort study.

OBJECTIVE: To investigate the time-courses of lung function and respiratory muscle pressure generating capacity after spinal cord injury. DESIGN: Multi-centre, prospective cohort study. SUBJECTS: One hundred and nine subjects with recent, motor complete spinal cord injury. METHODS: Lung function and respiratory muscle pressure generating capacity were measured at first mobilization, at discharge from inpatient rehabilitation and one year after discharge. Lung function was measured in all 109 subjects, and 55 of these performed additional measurements of respiratory muscle pressure generating capacity. Trajectories of respiratory muscle function for different lesion level groups were assessed by multi-variate multi-level regression models. RESULTS: Forced vital capacity, forced expiratory volume in 1 sec and maximal inspiratory muscle pressure generating capacity significantly increased during and after inpatient rehabilitation. Forced inspiratory volume in 1 sec, peak inspiratory flow, peak expiratory flow and maximal expiratory muscle pressure generating capacity increased only during inpatient rehabilitation, but not thereafter. Increasing lesion level had a negative effect on all measured lung function parameters, as well as on maximal inspiratory and expiratory muscle pressure generating capacity. CONCLUSION: Respiratory function improved during inpatient rehabilitation, but only forced vital capacity, forced expiratory volume in 1 sec and maximal inspiratory muscle pressure generating capacity further improved thereafter. In particular, expiratory muscle function and subjects with tetraplegia should be screened and trained regularly.     

Correlation of plasma beta-endorphin levels with mean arterial pressure and cardiac output in hypovolemic shock

Recent studies have been conducted to evaluate the relationship between plasma beta-endorphin (END) levels and the hemodynamic changes that occur in severely stressed animals. Using our canine hypovolemic shock model, END levels were analyzed during the baseline period, at the beginning of treatment (after a period of fixed-pressure hypovolemic shock), and at the end of treatment. Mean arterial pressure (MAP) and cardiac output were also measured at these intervals. Animals were given iv 5 ml of 0.9% NaCl, 4 mg/kg of naloxone (NAL), 30 mg/kg of methylprednisolone (MP), or 4 mg/kg of NAL and 30 mg/kg of MP. A fifth group was composed of nonsteroid-treated animals. Scatterplots were generated and linear regression lines were drawn comparing END with cardiac output and MAP. In the nonsteroid-treated animals, a significant correlation was found between decreases in both MAP and cardiac output and increasing levels of END. The addition of MP did not seem to alter the relationship, suggesting that MP did not affect END release.