Life-threatening Hypotension in a Multi-trauma-brain Injured Patient With Unilateral Adrenal Gland Damage; a Single Hydrocortisone Dose Unraveled Relative Corticosteroid Insufficiency.

BackgroundThe incidence of adrenal injury after trauma is very rare. Bilateral adrenal injury, which may lead to acute adrenal insufficiency and death, whereas unilateral adrenal trauma is often asymptomatic and masked by injuries to other organs. However, when unilateral adrenal trauma is associated with multiple injuries including brain trauma, critical illness‑related corticosteroid insufficiency (CIRCI) may be present; despite the importance, criteria for the diagnosis are not well established.Case presentationWe report a 16-year-old multi-trauma, brain-injured patient with unilateral adrenal gland injury. An intraparenchymal catheter for intracranial pressure (ICP) monitoring was inserted and craniectomy was performed. Postoperatively, the patient was admitted in the Intensive Care Unit (ICU) under sedation. He presented severe circulatory shock (noradrenaline dose of 1.86 μg/kg/min). which was not reversed despite red blood cell transfusions (noradrenaline increased to 2 μg/kg/min, lactate 1.8-2.1 mmol/L, although Hct was stabilized to 34 g/dl). Empiric hydrocortisone (150 mg intravenously) was administered for suspected adrenal insufficiency, after a blood sample for cortisol levels was drawn. An abrupt improvement in hemodynamics was noted [noradrenaline dose was reduced by half (1 μg/ kg/min) in less than 1 hour, and almost became insignificant during the next 8 hours, while lactate normalized (0.9 mmol/L)]. Hydrocortizone administration was continued for nine days. Fluid balance was restored after the first day. Baseline cortisol levels were 11.45 μg/dl. ICP was steadily less than 20 mmHg. Adrenal hematoma dimensions had increased (4 x 2.7 cm), as seen in the abdominal CT scan performed 9 hours after admission. Twenty days later, a follow up CT scan revealed regression of the hematoma. His remaining ICU course was complicated by fever and sepsis and remained in the ICU for 41 days.ConclusionAlthough, data do not support the use of empiric steroids in trauma patients (with or without brain injury), this case demonstrates that adrenal insufficiency must be considered in the differential diagnosis when shock exists; adrenal gland injury, even unilateral, may play an additional factor. An urgent decision is needed, that can influence outcome.

Critical illness-related corticosteroid insufficiency during difficult weaning from mechanical ventilation

Background Critical illness-related corticosteroid insufficiency (CIRCI) is common during critical illness and is usually associated with poor outcomes, as prolonged duration of mechanical ventilation (MV) and higher mortality. CIRCI may alter cardiac and vascular functions. Weaning-induced pulmonary oedema (WiPO) is a major mechanism of weaning failure. The aim of this study was to evaluate the role of CIRCI in patients with difficult ventilator weaning and its possible relation with WiPO. Methods This is a prospective study conducted in the intensive care of a university hospital in France. Patients under MV for more than 24 h, meeting weaning criteria and having failed the first spontaneous breathing trial (SBT) underwent a corticotropin stimulation test, with assessment of total blood cortisol levels immediately before (T0) 0.25 mg iv of tetracosactrin and 30 and 60 min afterward. Δmax was defined as the difference between the maximal value after the test and T0. CIRCI was defined as T0 < 10 μg/dL (276 nmol/L) and/or Δmax < 9 μg/dL (248 nmol/L) and inadequate adrenal reserve as Δmax < 9 μg/dL. Biomarkers (natriuretic peptide and protidemia) sampling and echocardiograms were performed during the second SBT and were used to diagnose WiPO, which was defined according to two definitions (one liberal and one conservative) derived from recent publications on the topic. Successful extubation was defined as patient alive without reintubation 7 days after extubation. A competing risk analysis was used to assess extubation failure and mortality. Results Seventy-six consecutive patients (63 ± 14 years; 49 men) with difficult weaning were enrolled. CIRCI and inadequate adrenal reserve occurred in 25 (33%) and 17 (22%) patients, respectively. The probability of successful extubation was significantly decreased in patients with CIRCI or inadequate adrenal reserve, as compared to their counterparts, and this association persisted after adjustment on severity (SOFA score at first SBT). WiPO occurred in 44 (58%) and 8 (11%) patients, according to the liberal and conservative definition, respectively. WiPO was not associated with CIRCI nor with inadequate adrenal reserve. Conclusion CIRCI was common during difficult weaning and was associated with its prolongation. We did not find a significant association between CIRCI and WiPO.

Critical Illness-related Corticosteroid Insufficiency is Common in Covid-19 and Treatment Provide Survival Benefit

PurposeCovid-19 is a severe lethal disease characterized with pneumonia and acute respiratory distress syndrome. We aimed to analyze the prevalence of critical illness-related corticosteroid insufficiency (CIRCI) in Covid-19 patients treated in intensive care unit and whether treatment of it would create any survival benefit. MethodsA total of 119 Covid-19 patients in intensive care unit were enrolled into the study. All patients received treatment for Covid-19 according to national guideline including hydroxychloroquine, favipiravir, antibiotics including azithromycin and oseltamivir in some patients. Basal cortisol below 10 µg/dl were accepted as CIRCI and above 34 µg/dl as intact HPA axis. Patients between them were introduced 1 µg cosynthropin stimulation test and delta cortisol below 9 µg/dl were also accepted as CIRCI. All patients who got diagnosis received hydrocortisone 300 mg/day until clinical condition stabilized. Mortality rate was recorded, then. ResultsCIRCI was detected in 50.4% of cases and mean plasma ACTH level was 14.8±6.0 pg/ml. Patients below age 65 had a statistically higher risk (63.4 % vs. 40.2%, p=0.012). Presence of comorbidity did not increase the risk of CIRCI (47.3% vs. 62.5%, p=0.18). Also, severity of pulmonary involvement and intubation did not increase the risk of CIRCI. Total mortality rate was 49.5% and not different in patients with and without CIRCI (45.0% vs. 54.5%, p=0.31) indicating benefit of corticosteroid treatment. ConclusionCIRCI is common in Covid-19 patients treated in intensive care unit and treatment of CIRCI provide survival benefit.

Corticosteroid receptor rebalancing alleviates critical illness-related corticosteroid insufficiency after traumatic brain injury by promoting paraventricular nuclear cell survival via Akt/CREB/BDNF signaling

Background We previously found that high-dose methylprednisolone increased the incidence of critical illness-related corticosteroid insufficiency (CIRCI) and mortality in rats with traumatic brain injury (TBI), whereas low-dose hydrocortisone but not methylprednisolone exerted protective effects. However, the receptor-mediated mechanism remains unclear. This study investigated the receptor-mediated mechanism of the opposite effects of different glucocorticoids on the survival of paraventricular nucleus (PVN) cells and the incidence of CIRCI after TBI. Methods Based on controlled cortical impact (CCI) and treatments, male SD rats (n = 300) were randomly divided into the sham, CCI, CCI + GCs (methylprednisolone 1 or 30 mg/kg/day; corticosterone 1 mg/kg/day), CCI + methylprednisolone+RU486 (RU486 50 mg/kg/day), and CCI + corticosterone+spironolactone (spironolactone 50 mg/kg/day) groups. Blood samples were collected 7 days before and after CCI. Brain tissues were collected on postinjury day 7 and processed for histology and western blot analysis. Results We examined the incidence of CIRCI, mortality, apoptosis in the PVN, the receptor-mediated mechanism, and downstream signaling pathways on postinjury day 7. We found that methylprednisolone and corticosterone exerted opposite effects on the survival of PVN cells and the incidence of CIRCI by activating different receptors. High-dose methylprednisolone increased the nuclear glucocorticoid receptor (GR) level and subsequently increased cell loss in the PVN and the incidence of CIRCI. In contrast, low-dose corticosterone but not methylprednisolone played a protective role by upregulating mineralocorticoid receptor (MR) activation. The possible downstream receptor signaling mechanism involved the differential effects of GR and MR on the activity of the Akt/CREB/BDNF pathway. Conclusion The excessive activation of GR by high-dose methylprednisolone exacerbated apoptosis in the PVN and increased CIRCI. In contrast, refilling of MR by corticosterone protects PVN neurons and reduces the incidence of CIRCI by promoting GR/MR rebalancing after TBI.

Critical Care Implications of Adrenal Disease States

Adrenal disease in the critically ill patient can present many challenges for the intensivist. Besides primary, secondary, and tertiary adrenal insufficiency, a state known as critical care–related corticosteroid insufficiency (CIRCI) has been described. Adrenal insufficiency can pose many issues to the critically ill patient as it can decrease the patient’s ability to respond to the stress that critical illness presents to the human body. Proper recognition and diagnosis of adrenal insufficiency in the critically ill patient can be extremely important in the treatment of these patients and could be a lifesaving intervention if CIRCI is discovered. A less commonly encountered issue of adrenal disease lies in the area of adrenal hormone excess caused by a pheochromocytoma or extra-adrenal paragangliomas. These tumors can release large amounts of endogenous catecholamines that cause significant patient morbidity and mortality if not recognized early and treated appropriately. Although adrenal insufficiency and adrenal excess are less commonly encountered problems in critically ill patients, the recognition and treatment of these disease states can prevent the morbidity and mortality of critically ill patients that suffer from these disease states. This review contains 5 figures, 5 tables, and 89 references. Key words: adrenal insufficiency, hypothalamic-pituitary axis, critical illness–related corticosteroid insufficiency, pheochromocytoma, steroid replacement therapy