Vasopressor Dependency Research Articles

Polymyxin B-immobilized fiber column hemoperfusion mainly helps to constrict peripheral blood vessels in treatment for septic shock.

BackgroundPolymyxin B-immobilized fiber column hemoperfusion (PMX) has been reported to be effective for patients with septic shock. It remains unclear, however, how the efficacy of PMX varies according to the characteristics and underlying conditions of the patients treated. The objective of the present study was to clarify the factors that result in clinical efficacy of PMX treatment.MethodsWe retrospectively investigated 78 consecutive patients with severe sepsis or septic shock who underwent PMX treatment. We reviewed the demographic data, routine biochemistry, microbiological data, infection focus, Acute Physiology and Chronic Health Evaluation (APACHE) II score, Sequential Organ Failure Assessment (SOFA) score, change in mean arterial pressure (MAP), inotropic score, vasopressor dependency index, plasma levels of endotoxin and lactate, PaO2/FIO2 ratio, and survival time. We also divided the patients into two groups for comparison, namely, those whose inotropic scores improved after PMX treatment (improvement group) and those whose inotropic scores did not improve (non-improvement group).ResultsThe inotropic score and the vasopressor dependency index significantly decreased from 18.1 to 9.9 (p < 0.05) and from 0.27 to 0.14 (p < 0.05), respectively, after PMX treatment in the overall study population, while no significant change in the PaO2/FIO2 ratio was observed (p = 0.96). The inotropic score at pre-PMX treatment was significantly higher in the improvement group than in the non-improvement group (p < 0.01). The improvement of the PaO2/FIO2 ratio after PMX treatment was significant in the improvement group (p < 0.05).ConclusionsThe improvement group’s inotropic score was higher, because of peripheral blood vessels dilatation and requirement for more catecholamines. Therefore, our study suggests that PMX treatment is particularly useful for improving hemodynamics in septic shock patients with excessively dilated peripheral blood vessels.

Prognostic factors in patients with septic shock in digestive surgery who have undergone direct hemoperfusion with polymyxin B-immobilized fibers: a retrospective observational study.

BackgroundDirect hemoperfusion with polymyxin B-immobilized fiber (PMX-DHP) has been widely used for patients with septic shock around the world, but the prognostic factors have not been fully understood. We conducted a retrospective analysis to determine the prognostic factors in patients with septic shock who underwent PMX-DHP.MethodsTwenty-nine patients with septic shock who underwent PMX-DHP were included in the study. The patients were divided into groups based on survival (n = 23) and non-survival (n = 6) 28 days after PMX-DHP, and the clinical data for the two groups before and after PMX-DHP were compared.ResultsIn non-survivors, the vasopressor dependency index before PMX-DHP was significantly higher (p = 0.046), and the leukocyte count before PMX-DHP was significantly lower (p = 0.024) than in survivors. Furthermore, base excess after PMX-DHP was significantly lower in non-survivors (p = 0.007) than in survivors. The optimal cutoff points of the vasopressor dependency index, leukocyte count, and base excess identified by receiver operating characteristic curves were 0.499/mmHg, 1360/μL, and −6.4 mmol/L, respectively. And the score using these three cutoffs, termed the prognostic score, was related to the prognosis of septic shock patients who underwent PMX-DHP (area under the curve = 0.946).ConclusionsThe prognostic score, using three parameters which are immediately and readily available in early phase after starting PMX-DHP, might be useful to predict the prognosis of these patients.

Therapeutic plasma exchange does not reduce vasopressor requirement in severe acute liver failure: a retrospective case series.

BackgroundIn acute liver failure (ALF) therapeutic plasma exchange (TPE) improves laboratory measures of liver function. In patients with ALF requiring minimal vasoactive support TPE has also been shown to provide haemodynamic benefits including an increase in systemic blood pressure. However the haemodynamic effects of TPE in patients with severe ALF requiring moderate or high dose vasopressor therapy has not been reported. We retrospectively examined the haemodynamic effects of TPE in a cohort of patients with severe ALF requiring vasopressor therapy.MethodsPhysiological, laboratory and treatment data were collected on all patients with ALF who received TPE between January 2000 and December 2012. All patients were managed in the intensive care unit of a tertiary referral centre for ALF and liver transplantation.The primary outcome measures were changes in mean arterial pressure (MAP), vasopressor score and the ratio of vasopressor score to MAP (vasopressor dependency index (VDI)) from baseline prior to TPE through to 12 hours after completion of TPE. Secondary outcome measures were changes in other routinely collected physiological variables and laboratory results. Results are presented as median (interquartile range (IQR)). Outcome measures were evaluated using a mixed effect model.ResultsThirty nine TPE were performed in 17 patients with ALF (13 paracetamol poisoning). All TPE were performed with a centrifugal apheresis system (duration 130 minutes (IQR 115 – 147.5), plasma volume removed 5.1% body weight (IQR 4.6 – 5.5). Baseline values for primary outcome measures were: MAP 82 mmHg (IQR 72 – 92.5), vasopressor score 8.35 (IQR 3.62 – 24.6) and VDI 0.10 (IQR 0.05 – 0.31).MAP was significantly higher immediately after TPE compared to baseline (p = 0.039), however when corrected for change in vasopressor requirement there was no significant change in VDI with TPE (p = 0.953). Twelve hours after TPE the MAP, vasopressor score and VDI were not significantly different from baseline (p = 0.563, p = 0.317 and p = 0.214 respectively).ConclusionIn this cohort of patients with severe ALF centrifugal TPE did not significantly affect vasopressor requirements.Electronic supplementary materialThe online version of this article (doi:10.1186/s12871-015-0017-9) contains supplementary material, which is available to authorized users.

Acute renal failure in cirrhotic patients with severe sepsis: Value of urinary interleukin‐18

Acute renal failure (ARF) is a common complication of liver cirrhosis and severe sepsis. Differentiating functional renal failure from acute tubular necrosis (ATN) has been difficult in this clinical setting. It has been shown that urinary interleukin 18 (IL-18) can serve as a sensitive marker for ARF and ATN. This study was aimed to investigate the diagnostic and prognostic values of urinary IL-18 in ARF associated with liver cirrhosis and severe sepsis. We prospectively evaluated the relationship between urinary IL-18 and clinical outcomes in 168 consecutive cirrhotic patients with severe sepsis. One hundred and eight patients (64.3%) developed ARF at admission to the intensive care unit. ARF was associated with higher urinary IL-18 and impaired effective arterial volume. Renal failure was functional in 64 (59.2%), due to acute tubular necrosis (ATN) in 30 (27.7%), and mixed type in 14 (12.9%). Patients with ATN had significantly higher levels of urinary IL-18, rates of vasopressor dependency, and hospital mortality than those with functional renal failure. By using the areas under receiver operating characteristic (AUROC) curve, urinary IL-18 demonstrated an excellent discriminative power (AUROC 0.882) for diagnosing tubular injury in those with ARF. Meanwhile, hospital survivors had significantly lower urinary and serum IL-18 levels, compared to non-survivors. In multivariate analysis, urinary IL-18, international normalized ratio, and mean arterial pressure were independent factors to predict hospital mortality. Urinary IL-18 can serve as a diagnostic and prognostic marker in cirrhotic patients with severe sepsis.

Therapeutic hypothermia and vasopressor dependency after cardiac arrest

ObjectiveClinical trials of therapeutic hypothermia (TH) after cardiac arrest excluded patients with persistent hemodynamic instability after return of spontaneous circulation (ROSC), and thus equipoise may exist regarding use of TH in these patients. Our objective was to determine if TH is associated with worsening hemodynamic instability among patients who are vasopressor-dependent after ROSC. MethodsWe performed a prospective observational study in vasopressor-dependent post-cardiac arrest patients. Inclusion criteria were age >17, non-trauma cardiac arrest, comatose after ROSC, and persistent vasopressor dependence. The decision to initiate TH (33–34°C) was made by the treating physician. We measured cumulative vasopressor index (CVI) and mean arterial pressure (MAP) every 15min during the first 6h after ROSC. The outcome measures were change in CVI (primary outcome) and MAP (secondary outcome) over time. We graphed median CVI and MAP over time for the treated and not treated cohorts, and used propensity adjusted repeated measures mixed models to test for an association between TH induction and change in CVI or MAP over time. ResultsSeventy-five post-cardiac arrest patients were included (35 treated; 40 not treated). We observed no major differences in CVI or MAP over time between the treated and not treated cohorts. In the mixed models we found no statistically significant association between TH induction and changes in CVI or MAP. ConclusionIn patients with vasopressor-dependency after cardiac arrest, the induction of hypothermia was not associated with a decrease in mean arterial pressure or increase in vasopressor requirement.

A Multicentre Study of Acute Kidney Injury in Severe Sepsis and Septic Shock: Association with Inflammatory Phenotype and HLA Genotype

BackgroundTo investigate the association between severity of acute kidney injury (AKI) and outcome, systemic inflammatory phenotype and HLA genotype in severe sepsis.Methodology/Principal FindingsProspective multicenter observational study done in 4 intensive care units in two university hospitals. Severe sepsis and septic shock patients with at least 2 organ failures based on the SOFA score were classified: 1) "no AKI", 2) "mild AKI" (grouping stage 1 and 2 of AKIN score) and 3) "severe AKI" (stage 3 of AKIN score). Sequential measurements: The vasopressor dependency index (VDI; dose and types of drugs) to evaluate the association between hemodynamic status and the development of early AKI; plasma levels of IL-10, macrophage migration inhibitory factor (MIF), IL-6 and HLA-DR monocyte expression. Genotyping of the 13 HLA-DRB1 alleles with deduction of presence of HLA-DRB3, -DRB4 and -DRB5 genes. We used multivariate analysis with competitive risk model to study associations. Overall, 176 study patients (146 with septic shock) were classified from AKIN score as "no AKI" (n = 43), "mild AKI" (n = 74) or "severe AKI" (n = 59). The VDI did not differ between groups of AKI. After adjustment, "mild and severe AKI" were an independent risk factor for mortality (HR 2.42 95%CI[1.01-5.83], p = 0.048 and HR 1.99 95%CI[1.30-3.03], p = 0.001 respectively). "Severe AKI" had higher levels of plasma IL-10, MIF and IL-6 compared to “no AKI” and mild AKI (p<0.05 for each), with no difference in mHLA-DR at day 0. HLA-DRB genotyping showed a significantly lower proportion of 4 HLA-DRB alleles among patients requiring renal replacement therapy (RRT) (58%) than in patients with severe AKI who did not receive RRT (84%) (p = 0.004).ConclusionsAKI severity is independently associated with mortality and plasma IL-10, MIF or IL-6 levels. Presence of 4 alleles of HLA-DRB in severe AKI patients seems associated with a lower need of RRT.

Early recovery in hemodynamics after direct hemoperfusion with polymyxin B-immobilized fibers may predict mortality rate in patients with septic shock

This retrospective and observational study attempted to determine whether the rapid improvement in hemodynamic parameters and the subsequent discontinuation or decrease of catecholamine infusion shortly after direct hemoperfusion with polymyxin B-immobilized fibers (PMX) may be strong predictors of mortality in patients with septic shock. Retrospectively, 46 patients were divided into two groups; those who survived more than 30days after PMX (survival group, S group) and those who died within 30days (nonsurvival group, NS group). Sequential Organ Failure Assessment (SOFA) scores, mean arterial pressure, catecholamine index (CAI), and vasopressor dependency index (VDI) were examined before and after PMX. The same parameters were examined on days 3, 4, 5, 6, 8, and 16 after PMX. CAI in the S group significantly decreased from 14.7 (95% CI, 10.3-19.1) at baseline to 6.4 (95% CI, 3.7-9.2; P<0.001) at post-PMX, whereas a significant decrease in CAI was not observed in the NS group (23.1; 95% CI, 15.4-30.7 to 18.1; 95% CI, 11.6-24.7; P=0.114). The significant decrease in VDI at post-PMX was observed both in the S group and in the NS group. If the cutoff point of VDI at post-PMX is 0.2, there is a significant difference in numbers of the S group (VDI≥0.2, n=24; VDI<0.2, n=2) and NS group (VDI≥0.2, n=8; VDI<0.2, n=20) using Fisher's exact test. We concluded that the early improvement in CAI and VDI shortly after PMX might be prognostic indicators for survival.

Fenoldopam use in a burn intensive care unit: a retrospective study.

BackgroundFenoldopam mesylate is a highly selective dopamine-1 receptor agonist approved for the treatment of hypertensive emergencies that may have a role at low doses in preserving renal function in those at high risk for or with acute kidney injury (AKI). There is no data on low-dose fenoldopam in the burn population. The purpose of our study was to describe our use of low-dose fenoldopam (0.03-0.09 μg/kg/min) infusion in critically ill burn patients with AKI.MethodsWe performed a retrospective analysis of consecutive patients admitted to our burn intensive care unit (BICU) with severe burns from November 2005 through September 2008 who received low-dose fenoldopam. Data obtained included systolic blood pressure, serum creatinine, vasoactive medication use, urine output, and intravenous fluid. Patients on concomitant continuous renal replacement therapy were excluded. Modified inotrope score and vasopressor dependency index were calculated. One-way analysis of variance with repeated measures, Wilcoxson signed rank, and chi-square tests were used. Differences were deemed significant at p < 0.05.ResultsSeventy-seven patients were treated with low-dose fenoldopam out of 758 BICU admissions (10%). Twenty (26%) were AKI network (AKIN) stage 1, 14 (18%) were AKIN stage 2, 42 (55%) were AKIN stage 3, and 1 (1%) was AKIN stage 0. Serum creatinine improved over the first 24 hours and continued to improve through 48 hours (p < 0.05). There was an increase in systolic blood pressure in the first 24 hours that was sustained through 48 hours after initiation of fenoldopam (p < 0.05). Urine output increased after initiation of fenoldopam without an increase in intravenous fluid requirement (p < 0.05; p = NS). Modified inotrope score and vasopressor dependency index both decreased over 48 hours (p < 0.0001; p = 0.0012).ConclusionsThese findings suggest that renal function was preserved and that urine output improved without a decrease in systolic blood pressure, increase in vasoactive medication use, or an increase in resuscitation requirement in patients treated with low-dose fenoldopam. A randomized controlled trial is required to establish the efficacy of low-dose fenoldopam in critically ill burn patients with AKI.

Relative adrenal insufficiency and hemodynamic status in cardiopulmonary bypass surgery patients. A prospective cohort study

BackgroundThe objectives of this study were to determine the risk factors for relative adrenal insufficiency in cardiopulmonary bypass patients and the impact on postoperative vasopressor requirements.MethodsProspective cohort study on cardiopulmonary bypass patients who received etomidate or not during anesthetic induction. Relative adrenal insufficiency was defined as a rise in serum cortisol ≤ 9 μg/dl after the administration of 250 μg of consyntropin. Plasma cortisol levels were measured preoperatively, immediately before, 30, 60, and 90 minutes after the administration of cosyntropin, and at 24 hours after surgery.Results120 elective cardiopulmonary bypass patients were included. Relative adrenal insufficiency (Δcortisol ≤9 μg/dl) incidence was 77.5%. 78 patients received etomidate and 69 (88%) of them developed relative adrenal insufficiency, (P < 0.001). Controlling for clinical characteristics with a propensity analysis, etomidate was the only independent risk factor associated with relative adrenal insufficiency (OR 6.55, CI 95%: 2.47-17.4; P < 0.001). Relative adrenal insufficiency patients showed more vasopressor requirements just after surgery (P = 0.04), and at 4 hours after surgery (P = 0.01). Pre and post-test plasma cortisol levels were inversely associated with maximum norepinephrine dose (ρ = -0.22, P = 0.02; ρ = -0.18, P = 0.05; ρ = -0.21, P = 0.02; and ρ = -0.22, P = 0.02, respectively).ConclusionsRelative adrenal insufficiency in elective cardiopulmonary bypass patients may induce postoperative vasopressor dependency. Use of etomidate in these patients is a modifiable risk factor for the development of relative adrenal insufficiency that should be avoided.

Can Circuit Lifetime be a Quality Indicator in Continuous Renal Replacement Therapy in the Critically Ill?

Continuous renal replacement therapy (CRRT) is frequently used in critically ill patients with acute renal failure and sepsis. Frequent circuit changes increase nursing workload, blood loss and costs, and also compromise achievement of the filtration rate goal. Circuit downtime is the most important factor that compromises the cumulative filtration goal. We used continuous venovenous hemodiafiltration (Prismaflex, Gambro, Meyzieu Cedex, France) in our 12-bed medical intensive care unit (ICU). Circuit lifetimes, indication to start CRRT anticoagulation protocol, reason for circuit change, and location of the vascular access were prospectively documented for 12 months in consecutive patients. Unfractionated heparin was the first choice for anticoagulation. No anticoagulation was used in patients with severe coagulation abnormalities or hepatic failure; regional citrate-based anticoagulation (CBA) was used in patients with recurrent circuit clotting or with bleeding predisposition. Our aim was to assess the suitability of circuit lifetime as a quality indicator, evaluated by survival analysis. Median circuit lifetime was significantly longer for CBA (log rank chi2 = 8.08; p = 0.018). This is consistent with the literature. There were no differences in vascular access site, proportion of sepsis, or vasopressor dependency between the three anticoagulation groups. In addition to monitoring the complication rate, the evaluation of circuit lifetime using survival analysis stratified by anticoagulation strategy is a simple and feasible means of assessing the quality of CRRT in the ICU.

Low serum concentration of apolipoprotein A-I is an indicator of poor prognosis in cirrhotic patients with severe sepsis

Severe sepsis is frequently associated with hypocholesterolemia which is also a common finding in cirrhotic patients. Lipoprotein is capable of binding endotoxin to which cirrhotic patients exhibit an excessive pro-inflammatory response. We evaluated the relationship between lipid levels, inflammatory cytokines and clinical outcomes in 103 cirrhotic patients with severe sepsis. The non-survivors had significantly lower concentrations of total cholesterol, high-density lipoprotein (HDL), and apolipoprotein A-I (APO A-I). HDL and APO A-I levels were inversely correlated with interleukin-6, tumor necrosis factor-alpha, and various disease severity scores. Serum creatinine, mean arterial pressure and low level of APO A-I (<47.5mg/dl) were independent factors to predict 90-day mortality. The cumulative survival rates at 90 days were 63.8% and 8.9% for the high APO A-I and low APO A-I groups (p<0.0001). Low APO A-I was also associated with lower mean arterial pressure, higher rate of vasopressor dependency, and greater plasma renin activity. Serum levels of HDL and APO A-I are inversely correlated with liver reserve and disease severity in cirrhotic patients with severe sepsis. Low level of APO A-I is associated with a marked impairment of effective arterial volume, multiple organ dysfunction and a poor prognosis.

Extended drotrecogin alfa (activated) therapy in patients with persistent requirement for vasopressor support after 96-hour infusion with commercial drotrecogin alfa (activated)

In the European Union, drotrecogin alfa (activated) (DAA) is licensed (intravenous infusion, 96 hours) for adults with severe sepsis with multiple organ failure. In the PROWESS trial, DAA treatment was associated with significant mortality reduction and more rapid improvement in cardiovascular function over 7 days (decreased need for vasopressors). But 22% of DAA-treated patients remained on vasopressors at end infusion. The primary aim of this study was to investigate, in severe sepsis patients with persistent vasopressor dependency at the end of 96-hour commercial DAA treatment, whether continued administration of DAA for up to a further 72 hours results in more rapid resolution of vasopressor dependency compared with placebo (no DAA after commercial DAA infusion). Secondary objectives were mortality, biomarker changes, and safety.

Adrenal exhaustion in septic patients with vasopressor dependency

Purpose The use of low-dose corticosteroids for patients with septic shock who remain vasopressor dependent after adequate fluid resuscitation is recommended, but there is lack of agreement on how to diagnose relative adrenal insufficiency (RAI) and when to start steroid supplementation among these patients. This case series reports changes in cortisol concentrations during the course of vasopressor-dependent septic shock. Methods Observational study was performed at a university hospital medical intensive care unit. Consecutive adult patients with vasopressor-dependent septic shock admitted to the medical intensive care unit were studied. Clinical data, cortisol concentrations, and dose of vasopressor agents at different times during the course of septic shock were recorded and reported as mean ± SD. Results Thirteen patients were included. Mean age was 59 ± 15 years. Mean basal nonstimulated cortisol level was 41.7 ± 30.9 μg/dL (within 24 hours of intensive care unit admission in all but 2 patients). Steroids were initiated in 8 patients and then discontinued after cortisol values were obtained and RAI was ruled out. Because of inability to discontinue vasopressor support, cortisol testing was repeated after 6.2 ± 4.8 days of initial assessment. Repeated concentrations were 10.0 ± 6.3 μg/dL ( P < .001). Steroids were then reinitiated, and resolution of vasopressor dependence was achieved 1.5 ± 1.4 days later. Conclusions Adrenal function in the critically ill is a dynamic process, and an appropriate initial adrenal response does not preclude later development of RAI.

Adrenal insufficiency in patients with cirrhosis, severe sepsis and septic shock†

Patients with cirrhosis are susceptible to bacterial infection, which can result in circulatory dysfunction, renal failure, hepatic encephalopathy, and a decreased survival rate. Severe sepsis is frequently associated with adrenal insufficiency, which may lead to hemodynamic instability and a poor prognosis. We evaluated adrenal function using short corticotropin stimulation test (SST) in 101 critically ill patients with cirrhosis and severe sepsis. Adrenal insufficiency occurred in 51.48% of patients. The patients with adrenal insufficiency had a higher hospital mortality rate when compared with those with normal adrenal function (80.76% vs. 36.7%, P < .001). The cumulative rates of survival at 90 days were 15.3% and 63.2% for the adrenal insufficiency and normal adrenal function groups, respectively (P < .0001). The hospital survivors had a higher cortisol response to corticotropin (16.2 +/- 8.0 vs. 8.5 +/- 5.9 microg/dL, P < .001). The cortisol response to corticotropin was inversely correlated with various disease severity, Model for End-Stage Liver Disease, and Child-Pugh scores. Acute physiology, age, chronic health evaluation III score, and cortisol increment were independent factors to predict hospital mortality. Mean arterial pressure on the day of SST was lower in patients with adrenal insufficiency (60 +/- 14 vs. 74.5 +/- 13 mm Hg, P < .001), and a higher proportion of these patients required vasopressors (73% vs. 24.48%, P < .001). Mean arterial pressure, serum bilirubin, vasopressor dependency, and bacteremia were independent factors that predicted adrenal insufficiency. In conclusion, adrenal insufficiency is common in critically ill patients with cirrhosis and severe sepsis. It is related to functional liver reserve and disease severity and is associated with hemodynamic instability, renal dysfunction, and increased mortality.

Analysis of blood glucose measurements using capillary and arterial blood samples in intensive care patients

To analyse agreement between two methods for blood glucose measurement in intensive care patients: capillary blood using a reagent strip and glucometer with arterial blood using a blood gas analyser. Prospective, single-centre, observational study in a 12-bed tertiary referral intensive care unit. Blood glucose levels were measured in consecutive patients using simultaneous measurements of capillary blood samples using glucometry and from a multi-electrode arterial blood gas analyser. An a priori subgroup of patients with tissue hypoperfusion was identified (defined as systolic blood pressure <90 mmHg or vasopressor dependency). A total of 493 paired measurements were obtained; 75 of these were from patients with systemic hypoperfusion. Overall, the mean difference (bias) was 0.12 mmol/l (2.15 mg/dl) and precision 0.77 mmol/l (13.8 mg/dl); 95% limits of agreement were -0.14 and 1.66 mmol/l (-2.5 and 29.8 mg/dl). In patients with systemic hypoperfusion the bias was 0.24 mmol/l (4.0 mg/dl) and precision 0.9 mmol/l (16.2 mg/dl); 95% limits of agreement -2.05 and 1.58 mmol/l (36.8 and 28.4 mg/dl). In a general population of intensive care patients, there is statistical agreement between blood glucose measured from capillary blood glucometry and arterial blood gas analysis. However, in patients with systemic hypoperfusion, the accuracy of agreement between these two measurement techniques may be such that that biochemical hypoglycaemia (<2.5 mmol/l, 44.9 mg/dl) may go undetected if used interchangeably.

Hypothalamic-pituitary-adrenal axis dysfunction in critically ill patients with traumatic brain injury: incidence, pathophysiology, and relationship to vasopressor dependence and peripheral interleukin-6 levels.

To investigate hypothalamic-pituitary-adrenal axis function in patients requiring mechanical ventilation for traumatic brain injury and to assess the relation of hypothalamic-pituitary-adrenal axis abnormalities with vasopressor dependence and peripheral cytokine levels. Prospective study. General intensive care unit in a university teaching hospital. Forty patients (33 men and 7 women) with moderate to severe traumatic brain injury (mean age, 37 +/- 16 yrs) were studied the day after termination of mechanical ventilation (7-60 days after trauma). First, a morning blood sample was obtained to measure baseline cortisol, corticotropin, interleukin-6, and tumor necrosis factor alpha. Subsequently, 1 microg of synthetic corticotropin was injected intravenously, and 30 mins later, a second blood sample was drawn to determine stimulated plasma cortisol. Based on data derived from healthy volunteers, patients having stimulated cortisol levels <18 microg/dL were defined as nonresponders to the low-dose stimulation test. Thirty-one patients underwent also a human corticotropin releasing hormone test. In traumatic brain injury patients, mean baseline and low-dose stimulation test-stimulated cortisol levels were 17.2 +/- 5.4 microg/dL and 24.0 +/- 6.6 microg/dL, respectively. The median increment in cortisol was 5.9 microg/dL. Basal corticotropin levels ranged from 3.9 to 118.5 pg/mL. Six of the 40 patients (15%) failed the low-dose stimulation test. The human corticotropin releasing hormone test (performed in 26 responders and five nonresponders) revealed diminished cortisol release only in the low-dose stimulation test nonresponder patients. Corticotropin responses to corticotropin releasing hormone were consistent with both primary (three patients) and/or secondary (two patients) adrenal dysfunction. In retrospect, nonresponders to the low-dose stimulation test more frequently required vasopressors (6/6 [100%] vs. 16/34 [47%]; p =.02) and for a longer time interval (median, 0 vs. 293 hrs; p =.006) compared with responders. Furthermore, nonresponders had higher interleukin-6 levels compared with responders (56.03 vs. 28.04 pg/mL; p =.01), whereas tumor necrosis factor alpha concentrations were similar in the two groups (2.42 vs. 1.55 pg/mL; p =.53). Adrenal cortisol secretion after dynamic stimulation is deficient in a subset of critically ill patients with moderate to severe head injury. This disorder is associated with prior vasopressor dependency and higher interleukin-6 levels.

Cortisol reserve in head trauma victims: evaluation with the low-dose (1 μg) corticotropin (ACTH) stimulation test

To investigate cortisol reserve in head trauma, 35 consecutive patients (30 men) with a mean age of 36 ± 16 years were studied 5–60 days after physical injury. Patients were enrolled in the study within a few days before ICU discharge. First, a morning blood sample was obtained to measure baseline cortisol, and ACTH plasma levels. Subsequently, 1 μg synthetic ACTH was injected intravenously and, 30 min later, a second blood sample was drawn to determine stimulated plasma cortisol. Patients having stimulated cortisol levels below 18 μg/dl were defined as nonresponders to the low-dose stimulation test (LDST). Mean (± SD) values for ACTH, baseline, and stimulated cortisol concentrations were 49 ± 27 pg/ml, 19.7 ± 5.5 μg/dl and 23.6 ± 6.7 μg/dl, respectively. Six of the 35 patients (17%) failed the LDST. Nonresponders were similar to responders with regard to age, gender, and severity of head injury. However, nonresponders more frequently required vasopressors (6/6 vs 14/29, P = 0.02) and for a longer time interval (median, 293 hours vs 24 hours, P = 0.01) to maintain haemodynamic stability compared with responders to the LDST. In conclusion, adrenal cortisol secretion following dynamic stimulation is deficient in a subset of head injury patients; this condition is associated with vasopressor dependency.

Treatment of cardiogenic shock and vasopressor dependency with intravenous methylphenidate (Ritalin)

Four patients are presented who had prolonged hypotension secondary to cardiogenic shock and who were dependent on vasopressor substances for maintenance of blood pressure. The intravenous administration of methylphenidate appeared to allow the withdrawal of vasopressors and the maintenance thereafter of a statisfactory blood pressure. The rapidity of action suggests that the drug works on a peripheral basis.