Assessment of adrenal function in cirrhotic patients using concentration of serum‐free and salivary cortisol

Objective: Because over 90% of serum cortisol is bound to albumin and corticosteroid‐binding globulin (CBG), changes in these proteins can affect measures of serum total cortisol levels in cirrhotics without altering serum‐free and salivary cortisol concentrations. Methods: We assessed basal (T₀) and post‐synacthen (T₆₀) serum total cortisol, serum‐free and salivary cortisol in 125 consecutive cirrhotics (95 non‐septic and 30 septic patients with a Child>8). Results: Serum total cortisol levels significantly decreased from the Child A–C non‐septic group, as did albumin and CBG levels, with a non‐significant rise in serum‐free cortisol concentrations. Non‐septic patients with low albumin (≤25 g/L) or CBG levels (≤35 mg/L) had lower T₀ serum total cortisol levels than patients with near‐normal albumin (303.4 vs. 382.6 nmol/L; P=0.0035) or with normal CBG levels (289.9 vs. 441.4 nmol/L; P<0.0001), respectively, despite similar serum‐free cortisol or salivary cortisol concentrations. Subnormal T₆₀ serum total cortisol concentrations (<510.4 nmol/L) were measured in 7.2% of all patients (Child C: 14.5% vs. Child A and B: 0%; P=0.0013) but no patients exhibited symptoms suggesting adrenal insufficiency. Patients with or without subnormal T₆₀ total cortisol had similar T₀ salivary cortisol and serum‐free cortisol concentrations. A trend was observed towards high serum‐free cortisol concentrations and mortality in multivariate analysis. Conclusions: Serum total cortisol levels overestimated the prevalence of adrenal dysfunction in cirrhotics with end‐stage liver disease. Since serum‐free cortisol cannot be measured routinely, salivary cortisol testing could represent a useful approach but needs to be standardized.     

Determination of salivary cortisol to assess time-related changes of the adrenal response to stress in critically ill patients

BackgroundThe value of salivary cortisol measurement to study stress-related adrenal response is controversial. The study aim was to assess the role of salivary cortisol measurement to detect time-related changes of adrenal response in critically ill patients.Patients and methodsPatients with organ failure, sepsis or trauma were prospectively recruited in the Emergency Department. Serum and salivary cortisol were measured at baseline (T0) and after 48 h (T48). In 33 patients ACTH test was also done.ResultsFifty-five patients were studied and classified as septic (22) or non-septic (33). We found a significant correlation between serum and salivary cortisol at T0 and T48. No patient had baseline serum cortisol < 276 nmol/L and salivary cortisol significantly decreased at T48 in almost all patients. A delta serum cortisol < 250 nmol/L after ACTH was found in only 4 patients who showed elevated baseline cortisol levels.ConclusionWe found that reduced baseline and post-ACTH cortisol levels are uncommon in our samples. In patients able to provide adequate saliva samples, salivary cortisol may be used to check the degree of stress-induced response and appears as a suitable tool for multiple measurements over time.     

Noninvasive assessment of cardiopulmonary function in critically ill infants and children

Echocardiography and Doppler echocardiography allow for the accurate noninvasive assessment of cardiac structure and function. Two-dimensional echocardiography accurately demonstrates both normal and abnormal intracardiac and great vessel anatomy and assists in differentiating cardiac from noncardiac causes of respiratory distress. M-mode echocardiography allows for documentation of cardiac chamber size and left ventricular function. Doppler echocardiography is used to measure cardiac output, assess AV and semilunar valve function, detect abnormal flow patterns within the heart and great vessels, and assist in the assessment of pulmonary artery pressures. This article discusses the uses of all these modalities as they apply to the critically ill infant and child.     

Diagnosis of adrenal failure in critically ill patients

In the last two decades there was important evolution on the knowledge of the function of the hypothalamic-pituitary-adrenal axis. In the last decade, the expression "relative adrenal insufficiency" (RAI) was created, and more recently "critical illness-related corticosteroid insufficiency" (CIRCI) was used to designate those patients in which cortisol production was not sufficiently increased in stress situations. Patients with CIRCI have elevated hospital morbidity and mortality. Currently, there is a wide discussion about diagnostic criteria for this dysfunction. Besides basal cortisol, some publications now study the role of other tests, such as cortrosyn test - either in low (1 μg) or high doses (250 μg); free cortisol, salivary cortisol, metyrapone test and others. With this review, we aimed at summarizing the results of the most influent papers that intended to define diagnostic criteria for CIRCI. We also suggest an approach for CIRCI diagnosis and make it clear that the decision about steroid therapy in septic shock patients is matter apart from RAI.     

Stress hyperglycemia and adrenal insufficiency in the critically ill

Critical illness evoked by trauma, extensive surgery, or severe medical illnesses is the ultimate example of acute severe physical stress. The endocrine response in a critically injured and stressed patient is varied and complex. Although the acute and chronic phases of critical illness are characterized by distinct endocrine responses, the diagnosis of these disorders is controversial. The inability to define the endocrine change as either adaptation or pathology renders the issue of treatment even more controversial. In addition, patients may have preexisting endocrine diseases, either previously diagnosed or unknown, and hence endocrine evaluation in a critically ill patient poses a major challenge to the health care provider. This review provides a novel insight into the dynamic endocrine alterations that occur during evolution of stress hyperglycemia and adrenal insufficiency in the critically ill patient and the available evidence for the therapy of these disorders.     

Urinary free cortisol is not a biochemical marker of hypertension

BACKGROUND: Increasing evidence suggests that glucocorticoids might play a role in blood pressure (BP) control. These reports show that cortisol (F) can increase the BP acting on the mineralocorticoid receptor in kidney, brain, heart, and blood vessel. The aim of this study was to evaluate the effects of F in the renal salt and water reabsorption in essential hypertensive patients (EH). METHODS: We studied 364 EH and 102 normotensive (NT) subjects. We obtained 24-h urine to measure urinary free cortisol (UFF) and creatinine (Cr). The upper limit of the UFF/Cr ratio was calculated from NT subjects. Patients with a high UFF/Cr ratio underwent dexamethasone suppression test (DST). Blood samples were used to determine plasma renin activity (PRA), aldosterone (SA), F, cortisone (E), urinary Na/K ratios, adrenocorticotrophic hormone levels, and also to purify lymphocytes for binding assays and genetic analysis. RESULTS: In EH subjects the UFF/Cr and F/E ratios were higher than in normotensives (48.3 microg/g [33.6 to 57.5 microg/g] v 32.6 microg/g [5.6 to 34.6 microg/g], P < .001 and 3.9 microg/g [3.3 to 4.8 microg/g] v 3.0 microg/g [2.4 to 3.6 microg/g], respectively), whereas the SA and PRA levels were similar. The upper limit value for UFF/Cr was set at 51.6 microg/g. The EH patients with high UFF/Cr (123/364, 34%) had lower PRA (1.5 ng/mL/h [0.9 to 2.5 ng/mL/h] v 2.0 ng/mL/h [1.1 to 3.0 ng/mL/h], P = .012, SA levels (7.1 ng/dL [4.1 to 10.5 ng/dL] v 7.9 ng/dL [5.2 to 11.0 ng/dL], P = .045) and Na/K ratios (3.6 [2.8 to 5.8] v 4.0 [3.1 to 6.6], P < or = .05) than those with normal UFF/Cr ratios. We found a slight negative relationship between UFF/Cr and PRA (r = -0.117, P = .031), SA (r = -0.096, P = .058) and Na/K ratios (r = 0.176, P = .059). We did not find significant differences in serum F/E ratios between EH patients with high or normal UFF/Cr (3.9 [3.3 to 5.1] v 3.8 [3.2 to 4.7], P = not significant [NS]) or a correlation between F/E ratio and UFF excretion (r = 0.032, P = NS). We did not find any association between UFF/Cr with systolic BP (P = .349) or diastolic BP (P = .895). Forty EH with the highest UFF/Cr values underwent the DST, which resulted in suppressed serum F in all of them. Binding assays in 4 of 13 EH with the highest UFF/Cr ratio showed a low affinity to dexamethasone (K(d) 13.7 to 33.0 nmol/L). The polymerase chain reaction (PCR) amplification of the GR gene (ligand-binding domain exons) did not show mutations or gross alterations. CONCLUSIONS: We found an EH subpopulation with abnormally high values of UFF but evidence of only a minor mineralocorticoid action, which was not directly related to the BP elevation, suggesting that another alternative mechanism could be triggering the F-induced hypertension. The origin of hypercortisoluria was not elucidated; however, a subtle glucocorticoid resistance was found in some cases.     

Clinical assessment of central venous pressure in the critically ill

To evaluate the accuracy of central venous pressure (CVP) assessment in critically ill patients, and measure disagreement amongst clinicians, 50 consecutive intensive care unit (ICU) patients with right internal jugular catheters were examined. CVP was measured by the indwelling catheter, and was assessed by: (1) one of three ICU staff physicians, (2) one of six medical residents, and (3) one of six medical students. There was no significant difference in CVP assessment between medical students, residents, and staff physicians. Although all clinicians tended to underestimate CVP, only the residents did so significantly (p less than 0.05). Sensitivity and specificity, and agreement and correlation between the clinicians' assessment and catheter measurements were higher when ventilated patients were excluded. All clinicians agreed more often and were better at identifying low CVP. In summary, considerable disagreement and inaccuracy exists in the clinical assessment of central venous pressure in critically ill patients.     

Effects of five parent-and-child risk factors on salivary cortisol levels and symptoms of posttraumatic stress disorder in school-age, critically ill children: Pilot study

Objective

We examined the contributions of risk factors to the psychological and neuroendocrine status of children admitted to a pediatric intensive care unit (PICU), and explored the feasibility of a full-scale study of these risk factors.

Methods

A prospective, correlational design was used. Risk factors included parental stress, parental anxiety, child anxiety, severity of the child's illness, and invasive procedures administered to the child. Outcomes variables were pediatric posttraumatic stress disorder (PTSD) symptoms and salivary cortisol levels. Measures were taken at 3 time points over 3 months.

Results

The mothers' state anxiety significantly increased over time, whereas the children's PTSD symptoms decreased. Most children with average or high anxiety demonstrated varying degrees of PTSD symptomatology, whereas children with low anxiety exhibited doubtful or mild symptoms of PTSD. As the severity of PTSD symptoms increased over time, the level of salivary cortisol decreased at two weeks and three months after hospital discharge.

Conclusions

Predicted trends in data were found and warrant further investigation, using a similar methodology in a full-scale study with an emphasis on recruiting the most seriously ill children.     

危重患者应激状态下血糖及皮质醇的变化分析

目的探讨危重患者应激状态下血糖及皮质醇的变化对病情发展以及预后的意义。方法将2008-02～2012-02收治的46例危重患者作为研究对象（主要为脏器功能衰竭者）,其中单脏器功能衰竭的设为观察A组（23例）,多脏器功能衰竭的设为观察B组（23例）,比较两组患者血糖以及相关激素的分泌情况和胰岛素量的使用情况。结果观察B组患者的血糖、血清胰岛素、皮质醇、胰高血糖素显著高于观察A组（P均〈0.01）,胰岛素的用量亦大于观察A组（P〈0.01）。结论危重患者在应激状态下血糖以及其相关激素的分泌会增加,对患者血糖和相关激素变化进行动态监测对判断患者的病情变化有一定的参考价值。     

The assessment of acute kidney injury in critically ill patients

Acute kidney injury (AKI) is common in critically ill patients and is associated with high morbidity and mortality. The availability of several biomarkers of kidney injury offers new tools for its early recognition and management. The early identification of high-risk patients provides an opportunity to develop strategies for the prevention, early diagnosis and treatment of AKI. Despite progress in critical care medicine over the past decade, the treatment strategies for AKI in critically ill patients, such as when to start renal replacement therapy, remain controversial. A recently proposed risk prediction score for AKI, based on routinely available clinical variables, presents a new means of identifying patients at high risk of AKI.     

Hyperreninemic hypoaldosteronism in the critically ill: a new entity

To define the changes in adrenal gland function during critical illness, we evaluated 28 severely ill patients with persistent hypotension who were hospitalized in a medical intensive care unit. The patients had increased plasma cortisol (mean +/- SE, 40.1 +/- 10.1 micrograms/dl). PRA was increased in all subjects (21.6 +/- 7.2 ng/ml.h); however, the plasma aldosterone concentration was inappropriately low in 18 of the subjects, with values ranging from 1-9 ng/dl, despite normal serum potassium concentrations (4.3 +/- 0.1 meq/liter) and increased concentrations of the aldosterone percursor, 18-hydroxycorticosterone. These 18 patients had hypotension associated with major infections and a high mortality rate (78%). Infusions of ACTH or angiotensin II were associated with a normal aldosterone response in only 2 of the 14 patients tested, also suggesting that the defect was probably at the level of the zone glomerulosa cell. Although infection was a common underlying illness, no other factors, such as dopamine administration, decreased angiotensin-converting enzyme activity, or increased aldosterone clearance, could be implicated as the cause of the phenomena. Thus, selective hypoaldosteronism in the presence of high renin levels exists in a substantial percentage of hypotensive critically ill patients.     

Intravascular catheter-related infections: a preventable challenge in the critically ill

In modem medicine, central venous catheters (CVCs) have a pivotal role in the management of critically ill patients. The most serious complication of effective CVC placement is catheter-related bloodstream infection (CRBSI). Microbial colonization and CRBSI are the byproducts of the interaction of 4 factors: (1) microbial factors (hydrophobicity and exopolysaccharide production), (2) host factors (such protein adhesins as fibrin and fibronectin that attach to the catheter surface), (3) catheter material (hydrophobicity, surface charges, thrombogenicity), and (4) iatrogenic factors (total parenteral nutrition, interleukin-2). The organisms most frequently associated with CRBSI are Staphylococcus epidermidis, Staphylococcus aureus, and Candida spp. CRBSIs were traditionally diagnosed through semiquantitative or quantitative cultures of the catheter tip. However, the diagnosis can be achieved without catheter removal through cultures of blood specimens collected simultaneously though the CVC and a peripheral vein. Currently, the most effective method of preventing a CRBSI is the use of a CVC coated with antimicrobial agents. Intravenous administration of vancomycin for 7 days is adequate for an uncomplicated CRBSI caused by coagulase-negative staphylococci, and at least 10 days of therapy with beta-lactams is required for an uncomplicated infection caused by methicillin-sensitive S. aureus. CRBSI caused by Candida albicans or Candida parapsilosis can be treated with at least 14 days of therapy with fluconazole or amphotericin B. In the case of Candida krusei, only amphotericin B is effective.     

Effect of metoclopramide--a dopaminergic blocker and endogenous cortisol on TSH secretion in critically ill men

In 17 critically ill men, low levels of FT4, TT4, TT3 and elevated levels of rT3 and cortisol were found. In spite of the low levels of circulating thyroid hormones, TSH levels of the critically ill men were significantly lower than those of the control group, with no correlations to the high cortisol levels. After iv injection of metoclopramide (MCP), a dopamine (DA) receptor blocker, the TSH and prolactin (Prl) increments in the critically ill patients were significantly lower than in the controls. No correlation was observed between basal cortisol levels and integrated TSH response to MCP. It is suggested that increased DA tone or high cortisol levels are not responsible for the lower basal TSH levels and for the blunted TSH or Prl responses to MCP in the critically ill. High levels of cortisol may be responsible for the altered TT4 peripheral metabolism to TT3 and rT3 in these patients.