Stress-dose Corticosteroids Research Articles

Evaluation of Serum Cortisol Levels and Response to Cosyntropin Test in Methadone-treated Opium Addicts.

Opium has been used for thousands of years for medical and analgesic purposes, and its misuse has also increased in recent years. Methadone, a synthetic opioid, has been used as an analgesic and to help patients quit opium addiction. However, some evidence suggests that long-term use of opioids can affect the hypothalamic-pituitary-adrenal axis. We aimed to evaluate the serum cortisol level and response to the cosyntropin stimulation test in opium addicts on methadone treatment. The study was conducted in November 2019 at Imam Reza Hospital Rehab Center, Birjand, Iran. Thirty-eight methadone-treated opium addicts participated in the study. A blood sample was initially obtained, then 250 µg intramuscular cosyntropin was injected. After 30 and 60 minutes, two other blood samples were obtained. The data were analyzed using SPSS. There was a significant difference between serum cortisol levels and the normal value in methadone users (9.46 ± 5.42 vs. 14 µg/dL) (P < 0.001). The mean response to the cosyntropin stimulation test in methadone users was 9.34 ± 8.11 µg/dL. Also, 55% of the participants had adrenal insufficiency. Serum cortisol levels significantly differed from normal values in methadone-treated patients. Therefore, we recommend measuring serum cortisol levels in methadone-treated patients before major medical procedures to consider the stress doses of corticosteroids.

728: OUTCOMES AND TIMING OF STRESS-DOSE HYDROCORTISONE IN PEDIATRIC SEPTIC SHOCK

Introduction: Sepsis is a major contributor to pediatric morbidity and mortality worldwide. Pediatric sepsis is defined as systemic inflammatory response syndrome (SIRS) in the presence of suspected or confirmed infection. Pediatric septic shock is defined as sepsis with cardiovascular organ dysfunction. In vasoactive-inotropic recalcitrant septic shock, stress dose corticosteroids are often administered for presumed critical illness related corticosteroid insufficiency (CIRCI). However, there is not consistent data to support the use of stress dose hydrocortisone (HCT) in septic shock. To further investigate clinical outcomes related to timing of HCT, we hypothesized that children with vasoactive-inotropic recalcitrant septic shock who received early HCT (< 6 hours) would have lower vasoactive-inotropic scores (VIS) in the first 48 hours, a decreased length of stay (LOS) and increased ventilator-free days (VFD). Methods: A retrospective chart review was performed from November 2017 to December 2021 of subjects 0 to < 18 years, admitted to the pediatric intensive care unit (PICU) meeting the definition for septic shock, requiring vasopressors and/or inotropes and given HCT for CIRCI. We measured VIS, PICU and hospital LOS and VFD. Subjects with chronic steroid use or who received etomidate were excluded. Results: Of 227 subjects screened, 23 met criteria for analysis. Seven subjects received HCT within 6 hours of vasopressor initiation (early group), while 16 received HCT >6 hours (late group). Initial VIS average was 10.96 in the early group and 10.78 in the late group. At 48 hours, average VIS in the early group was 9.51 and 1.44 in the late group. Average PICU LOS was 15.58 for the early group and 10.82 for the late group. Average hospital LOS was 37.47 for the early group and 19.76 for the late group. VFD average was 15.32 in the early group and 16.61 in the late group. Pediatric Index of Mortality 3 (PIM-3) average in the early group was 2.02 and 1.61 in the late group. Mortality incidence was 2 in 7 in the early group, and 4 in 16 in the late group. Conclusions: Preliminary data suggests there is an increased VIS at 48 hours, increased PICU and hospital LOS, and decreased VFD with early administration of HCT. Although PIM-3 scores were higher in the early group, mortality was similar between groups.

LBODP108 Did You Follow Your Patient After ICI Cessation? A Case of Immune-Related Adverse Event 5 Months Following Completion Of Immunotherapy

Abstract Introduction Immune checkpoint inhibitors (ICI) have been approved for use in cancer therapy for malignant melanoma, non-small cell lung cancer, and renal cell carcinoma in the last decade. Since their inception, immune-related adverse events (irAEs) have been well documented. We present a patient who developed 2 irAEs - grade 1 irAE during therapy and grade 3 irAE five months after completion of anti-CTLA-4 (Ipilimumab) and anti-PD-1 antibody (Nivolumab) therapy. Case description Our patient is a 65-year-old woman who was diagnosed in 2019 with Melanoma over the left knee which was resected in her home country. During follow-up here, she was started on immunotherapy with Ipilimumab and Nivolumab for metastatic disease. Her baseline labs including TFTs were normal before initiation of therapy. During treatment after 4 infusions, she developed hypothyroidism. At that time she was tolerating treatment well. Levothyroxine was initiated for this grade 1 irAE with the continuation of immunotherapy. She decided to move to her home country with a plan to pursue further immunotherapy upon her return. 7 months after discontinuation of therapy, the patient presented to our hospital with nausea, vomiting, and dizziness for 2 months. She was hypotensive and minimally responsive to intravenous fluids. Labs drawn were remarkable for hypothyroidism. Further workup demonstrated adrenal insufficiency with morning cortisol of 0.1 μg/dL and ACTH of &amp;lt;1.5 pg/ml. Pituitary hormones were within normal range except for elevated prolactin. A contrast-enhanced MRI of the pituitary was negative for any enlargement or mass. She was diagnosed with secondary adrenal insufficiency and managed with stress-dose corticosteroids with a resolution of symptoms. We were able to ascertain that our patient developed grade 3 irAE almost 5 months after her last immunotherapy. Discussion Cancer immunotherapy is associated with endocrinopathies such as hypophysitis, hypothyroidism, and adrenal insufficiency. As per a review done by González-Rodríguez E et al it has been found that the median time of onset from initiation for endocrine AEs was 7 - 20 weeks due to Ipilimumab and 11 weeks due to Nivolumab. In patients who received combined therapy, as per a retrospective study done by Nguyen et al, the median time from ICI administration to the diagnosis of immune-related hypophysitis was 35.8 weeks. In 2019, Ohara N reported a case of a patient with lung adenocarcinoma who developed isolated ACTH deficiency 4 months after discontinuation of Nivolumab therapy. Our patient developed two irAEs - during and after completion of immunotherapy. Symptoms can often be generalized and overlap with those of cancer progression making it difficult to diagnose. Our case highlights the need for continued surveillance of these patients by physicians probably even months after completion. Presentation: No date and time listed

Physiologic effects of stress dose corticosteroids in in-hospital cardiac arrest (CORTICA): A randomized clinical trial

AimPostresuscitation hemodynamics are associated with hospital mortality/functional outcome. We sought to determine whether low-dose steroids started during and continued after cardiopulmonary resuscitation (CPR) affect postresuscitation hemodynamics and other physiological variables in vasopressor-requiring, in-hospital cardiac arrest. MethodsWe conducted a two-center, randomized, double-blind trial of patients with adrenaline (epinephrine)-requiring cardiac arrest. Patients were randomized to receive either methylprednisolone 40 mg (steroids group) or normal saline-placebo (control group) during the first CPR cycle post-enrollment. Postresuscitation shock was treated with hydrocortisone 240 mg daily for 7 days maximum and gradual taper (steroids group), or saline-placebo (control group). Primary outcomes were arterial pressure and central-venous oxygen saturation (ScvO2) within 72 hours post-ROSC. ResultsEighty nine of 98 controls and 80 of 86 steroids group patients with ROSC were treated as randomized. Primary outcome data were collected from 100 patients with ROSC (control, n = 54; steroids, n = 46). In intention-to-treat mixed-model analyses, there was no significant effect of group on arterial pressure, marginal mean (95% confidence interval) for mean arterial pressure, steroids vs. control: 74 (68–80) vs. 72 (66–79) mmHg] and ScvO2 [71 (68–75)% vs. 69 (65–73)%], cardiac index [2.8 (2.5–3.1) vs. 2.9 (2.5–3.2) L/min/m2], and serum cytokine concentrations [e.g. interleukin-6, 89.1 (42.8–133.9) vs. 75.7 (52.1–152.3) pg/mL] determined within 72 hours post-ROSC (P = 0.12–0.86). There was no between-group difference in body temperature, echocardiographic variables, prefrontal blood flow index/cerebral autoregulation, organ failure-free days, and hazard for poor in-hospital/functional outcome, and adverse events (P = 0.08–>0.99). ConclusionsOur results do not support the use of low-dose corticosteroids in in-hospital cardiac arrest.Trial Registration:ClinicalTrials.gov number: NCT02790788 (https://www.clinicaltrials.gov).

Clinical Utilization of Stress Dose Hydrocortisone in Adult Patients With Septic Shock: A Retrospective Observational Study at a Large Academic Medical Center

Background: The use of stress dose corticosteroids, specifically, hydrocortisone, in septic shock is heterogeneous, and current clinical trials yield conflicting results. Regardless, they are still recommended by guidelines for vasopressor-dependent septic shock. Objectives: This study sought to characterize current practice of hydrocortisone use in patients with septic shock and secondarily to compare clinical outcomes of those who received hydrocortisone to those who did not. Methods: This single center, retrospective cohort study evaluated patients with septic shock admitted to a tertiary care center between 2012 and 2017. Patients receiving hydrocortisone for at least two doses were compared to those without. Results: 3411 septic shock patients were included; 1593 (47%) received hydrocortisone and 1818 (53%) did not. Patients who received hydrocortisone had higher lactate (4.0 vs 3.4 mmol/L; P < .01) and Acute Physiology and Chronic Health Evaluation (APACHE) III scores (104.1 vs 91.0; P < .01). Vasopressor duration was 1.7 days longer in the hydrocortisone group (P < .01), and the hydrocortisone group had higher hospital mortality (52% vs 38%; P < .01). A propensity score–matched population was conducted in patients with APACHE scores >100: vasopressor duration was longer in those who received hydrocortisone (3.9 vs 2.0 days; P < .01), and hospital mortality was higher (59.3% vs 53.1%; P = .036); however, after multivariable adjustment, no association between receipt of hydrocortisone and hospital mortality was detected (OR 1.2 [95% CI .9–1.6]). Conclusions: Patients who received hydrocortisone were more severely ill than those that did not, making retrospective evaluation of this question challenging. These results highlight the wide variability and heterogeneity in hydrocortisone use in clinical practice.

Perioperative stress dose steroid management of children with classical congenital adrenal hyperplasia: Too much or too little?

Children with congenital adrenal hyperplasia (CAH) are at risk for adrenal crises in the perioperative period and require higher doses of glucocorticoids. However, there are no specific protocols detailing the appropriate stress dosing required for children with CAH undergoing surgery with anesthesia. To evaluate CAH patients using our current hydrocortisone stress dose surgical protocol. We hypothesized that current clinical protocols may overestimate the endogenous response to perioperative stress. 14 children with CAH scheduled to have genital surgery and a control group of 10 unaffected children scheduled to have cardiac or urologic surgery (of a similar duration) were evaluated in a prospective observational study. Urinary free cortisol (UFC) and urinary 17-hydroxycorticosteroids (17-OHCS) per body surface area were measured in the postoperative period. UFC levels were significantly higher in CAH patients (115.8±24.6nmol/m2) than in controls (26.5±12.2nmol/m2), P<0.05.17-OHCS levels were also higher in CAH patients than in controls (6.5±0.5nmol/m2 vs. 3.4±0.5nmol/m2), P<0.05). In the immediate postoperative period, urinary cortisol and its metabolites are significantly higher in pediatric CAH patients receiving stress dose corticosteroids compared to controls. Results suggest that the amount of hydrocortisone given during our stress dose protocol may be higher than physiologic needs. Future dynamic studies are needed to determine appropriate perioperative and postoperative cortisol requirements in pediatric CAH patients in order to develop optimal stress dose regimens.

Plasmapheresis as First Line Therapy for Thyrotoxicosis in a Critically Ill Patient

Introduction: The role of plasmapheresis (TPE) in thyrotoxicosis management is not well established. Its use may be determined on an individualized basis (1). We report a case of a critically ill patient where TPE was utilized as first-line therapy for refractory thyrotoxicosis. Clinical Case: A 33-year-old woman with Graves’ disease complicated by medication non-adherence presented with rapidly ascending paralysis and bulbar weakness. Primary work up was consistent with acute inflammatory demyelinating polyneuropathy (AIDP) based on EMG findings of motor fiber polyneuropathy with demyelinating features. Laboratory evaluation revealed uncontrolled hyperthyroidism (TSH <0.05 uU/mL, N 0.3-4.2 uU/mL; fT4 3.9 ng/dL, N 0.6-1.5 ng/dL; tT3 318, N 60-160 ng/dL). Initially, there was low concern for thyrotoxicosis based on a Burch-Wartofsky score of 15 (2). Standard dose methimazole and aggressive beta-blockade were initiated. Hospital course was complicated by hypoxic respiratory failure due to progressive paralysis requiring intubation and septic shock from Klebsiella pneumonia requiring initiation of pressors and broad-spectrum antibiotics. Biochemical evaluation showed increasing fT4 (3.8 ng/dL) and tT3 (419 ng/dL) levels. Burch-Wartofsky score increased to 55, consistent with a thyrotoxic crisis. Due to the patient’s critical condition, TPE was rapidly initiated along with standard therapy for thyrotoxic crisis (high dose methimazole, esmolol drip, stress dose corticosteroids, cholestyramine, and potassium iodide) as a bridge to definitive management with thyroidectomy. Rapid clinical improvement with a decline in fT4 levels (3.8 to 2.1 ng/dL) was noted after initiation of TPE with normalization in fT4 (1.5 ng/dL) and tT3 (54 ng/dL) after three sessions. Thyroidectomy was pursued after clinical stabilization. Surgical pathology showed diffuse papillary hyperplasia consistent with Graves’ disease. Due to persistent respiratory failure, the patient underwent tracheostomy placement. Repeat EMG revealed severe myopathic dysfunction without demyelinating features favoring a diagnosis of acute thyrotoxic myopathy over AIDP. Patient was ultimately discharged to a long term acute care facility due to slow neurological recovery. Conclusion: TPE should be considered as first line management in conjunction with conventional medical therapy in critically ill patients with thyrotoxicosis as a bridge to thyroidectomy due to rapid time to effect and patient stabilization.

Corticosteroids Replacement in a Patient With Panhypopituitarism and COVID-19 Infection

Background: Hypopituitarism refers to complete or partial insufficiency of pituitary hormone secretion and patients require lifelong hormone replacement. Those with ACTH deficiency rely on exogenous glucocorticoids and at times of intercurrent illness require stress doses to prevent an adrenal crisis. The benefits and adverse effects of corticosteroids for treatment of COVID-19 pneumonia are currently under investigation. We report our experience in a patient with COVID-19 pneumonia who received high dose corticosteroids for panhypopituitarism. Clinical Case: A 51-year-old man presented with one-week history of fever and generalized weakness. He had been diagnosed with a non-functional pituitary macro-adenoma causing panhypopituitarism 1 year ago when he developed generalized tonic-clonic seizures. He underwent trans-sphenoidal resection of the pituitary adenoma. However, he then discontinued his hormonal therapy and was lost to follow up. He had postural hypotension but was not tachypneic or hypoxemic. He tested positive for COVID-19 and chest x-ray showed prominent bilateral broncho-vascular markings; he was hospitalized as mild COVID-19 pneumonia. Laboratory investigations revealed secondary adrenal insufficiency, secondary hypothyroidism and hypogonadotropic hypogonadism. MRI of the pituitary now showed persistence of the pituitary macroadenoma, measuring 3.5 x 3.7 x 2.4 cm in dimensions, causing sellar obliteration and left cavernous sinus invasion. Treatment with stress dose steroids, Hydrocortisone 50 mg 4 times daily was initiated, followed by thyroid hormone replacement with Levothyroxine 125 mcg daily. He also received antivirals andsupportive care for COVID-19, guided by local hospital protocol. After significant clinical improvement, steroids were tapered down and he was discharged on a maintenance dose of 20 mg hydrocortisone per day in divided doses. The patient was stable at outpatient follow up after one month. He was started on testosterone replacement for erectile dysfunction due to hypogonadotropic hypogonadism. He was offered surgery for complete resection of the residual pituitary adenoma, but he declined and preferred to continue medical therapy. Conclusion: Hypopituitarism is associated with significant morbidity and premature mortality, a key risk factor being cortisol deficiency. Adrenal crisis is a life-threatening medical emergency and remains an important cause of death in patients with adrenal insufficiency. These patients are also vulnerable to develop severe complications from COVID-19 infection due to the absence of normal cortisol responses to stress. Despite receiving stress dose corticosteroids, this high-risk patient recovered from COVID-19 pneumonia without complications. These findings support the use of corticosteroids when necessary for treatment of coexisting conditions in patients with COVID-19.

Dual Adenomas: Detection of Cushing’s Syndrome of Adrenal Origin During Evaluation of Pituitary Macroadenoma

Abstract Cushing’s syndrome is a rare and often severe disease associated with increased mortality and major metabolic complications with cardiovascular disease as the main cause of death. Adrenal masses are most often found by radiographic studies or autopsy as incidentalomas. The prognosis of Cushing’s syndrome is mainly affected by the difficulties in timely diagnosis and treatment of the disease, which remain a challenge due to its nonspecific presentation and multitude of etiologies. Herein, we present an atypical case of adrenal Cushing’s syndrome unveiled by the workup of a nonfunctioning pituitary macroadenoma. A 62 year-old woman presented with new intermittent headaches and worsening vision changes for the past year. She was found to have a large sellar mass measuring 2.7 x 2.4 x 3.0 cm invading the right cavernous sinus with displacement of the optic chiasm on brain magnetic resonance imaging (MRI). In the interim to neurosurgical evaluation, lab work performed to assess pituitary function showed an elevated late night salivary cortisol at 0.200 UG/DL (0.010–0.090 UG/DL range). Low early morning ACTH and elevated late night salivary cortisol, dexamethasone suppression test and 24 hour urine cortisol were observed and confirmed with repeat studies. These findings warranted a computed tomography (CT) adrenal mass protocol which revealed a left adrenal lesion consistent with a lipid rich adenoma measuring 4.9 x 3.5 x 4.1 cm in size. Subsequent urine catecholamines and metanephrines were within normal limits. The patient was admitted for transphenoidal pituitary resection with perioperative stress dose corticosteroids, but was only able to achieve partial resection due to large tumor size. Post-operatively the patient did well on a quick corticosteroid taper down to hydrocortisone 15 mg in AM and 5 in afternoon with hope to wean in the near future. Post-operative workup showed ACTH 4.6 pg/mL (7.2 – 63.3 pg/mL) and 8 am cortisol 24.7 MCG/DL (6.2–19.4 MCG/DL) which suggests autonomous adrenal secretion of cortisol. Once the patient has recovered from her partial pituitary resection she will be referred to general surgery for adrenalectomy. This case provided a review of a classic pituitary macroadenoma workup with an interesting twist to Cushing’s etiology as the cause was not from the pituitary as originally thought.

Lung Injury After Neonatal Congenital Cardiac Surgery Is Mild and Modifiable by Corticosteroids

The present study was performed to determine whether lung injury manifests as lung edema in neonates after congenital cardiac surgery and whether a stress-dose corticosteroid (SDC) regimen attenuates postoperative lung injury in neonates after congenital cardiac surgery. A supplementary report of a randomized, double-blinded, placebo-controlled clinical trial. A pediatric tertiary university hospital. Forty neonates (age ≤28 days) undergoing congenital cardiac surgery with cardiopulmonary bypass. After anesthesia induction, patients were assigned randomly to receive intravenously either 2 mg/kg methylprednisolone or placebo b, which was followed by hydrocortisone or placebo bolus six hours after weaning from CPB for five days as follows: 0.2 mg/kg/h for 48 hours, 0.1 mg/kg/h for the next 48 hours, and 0.05 mg/kg/h for the following 24 hours. The chest radiography lung edema score was lower in the SDC than in the placebo group on the first postoperative day (POD one) (p = 0.03) and on PODs two and three (p = 0.03). Furthermore, a modest increase in the edema score of 0.9 was noted in the placebo group, whereas the edema score remained at the preoperative level in the SDC group. Postoperative dynamic respiratory system compliance was higher in the SDC group until POD three (p < 0.01). However, postoperative oxygenation; length of mechanical ventilation; and tracheal aspirate biomarkers of inflammation and oxidative stress, namely interleukin-6, interleukin-8, resistin, and 8-isoprostane, showed no differences between the groups. The SDC regimen reduced the development of mild and likely clinically insignificant radiographic lung edema and improved postoperative dynamic respiratory system compliance without adverse events, but it failed to improve postoperative oxygenation and length of mechanical ventilation.

Critical Low Catastrophe: A Case Report of Treatment-Refractory Hypoglycemia following Overdose of Long-Acting Insulin

Overdose of long-acting insulin can cause unpredictable hypoglycemia for prolonged periods of time. The initial treatment of hypoglycemia includes oral carbohydrate intake as able and/or parenteral dextrose infusion. Refractory hypoglycemia following these interventions presents a clinical challenge in the absence of clear guidelines for management. Octreotide has sometimes been used, but its use is generally limited to sulfonylurea overdose. In this case report, we present a case of refractory hypoglycemia following an overdose of 900 units of long-acting insulin glargine that failed to respond to usual modes of therapy mentioned above. Stress-dose corticosteroids were then initiated, followed by subsequent improvement in IV dextrose and glucagon requirements and blood glucose levels. Hence, corticosteroids may serve as an adjunctive therapy in managing hypoglycemia and can be considered earlier in the course of treatment in patients with refractory hypoglycemia to prevent volume overload, especially when large volumes of dextrose infusions are required.

SUN-308 Central Adrenal Insufficiency Is Rare in Adults with Prader-Willi Syndrome

Introduction: Prader-Willi syndrome (PWS) is associated with several hypothalamic-pituitary hormone deficiencies. There is no agreement on the prevalence of central adrenal insufficiency (CAI) in adults with PWS. This is partly due to the variable results of the synacthen test, compared with the more robust metyrapone test (MTP) and insulin tolerance test (ITT). In some countries, patients with PWS receive stress-dose corticosteroids during physical or psychological stress. Side effects of frequent corticosteroids use are weight gain, osteoporosis, diabetes mellitus and hypertension, already major problems in adults with PWS. However, undertreatment of CAI can cause significant morbidity or even mortality. To prevent over- and undertreatment with corticosteroids, we assessed the prevalence of CAI in a large international cohort of adults with this rare disorder. Methods: The hypothalamic-pituitary-adrenal axis was tested in 81 adult subjects (55 Dutch, 10 British, 10 French, 6 Swedish) with genetically confirmed PWS. For multiple-dose MTP, 11-deoxycortisol >230 nmol/L (7.6 g/dL) was considered sufficient. For Dutch, French and Swedish patients who underwent ITT, cortisol >500 nmol/L (18.1 μg/dL) was considered sufficient. For British patients cortisol >450 nmol/L (16.3 μg/dL) was considered sufficient, as this center used a different assay. Additionally, we reviewed medical files of 645 adults with PWS from Italy (240), France (110), the Netherlands (110), Australia (60), Spain (45), Sweden (38) and the United Kingdom (42) for symptoms of hypocortisolism/adrenal crisis during surgery. Results: Data on 81 adult subjects (46 males and 35 females), median age (range) 25.2 yr (18.0 – 55.5), median BMI (range) 29.1 kg/m2 (20.0 – 62.0), with genetically confirmed PWS were collected. 33 subjects (41%) were using GH treatment since childhood. Multiple-dose MTP was performed in 45 subjects and ITT in 36 subjects. Both tests were well tolerated by all individuals. CAI was excluded in 80 of 81 patients. One patient with a peak cortisol level of 494 nmol/L (just below cut-off level of 500 nmol/L) was prescribed hydrocortisone for use during physical stress. There was no relation between baseline cortisol and ITT/multiple-dose MTP results. Even patients with a low baseline cortisol level (lowest: 102.0 nmol/L) had normal responses. Among the 645 patients whose medical files were reviewed, 200 had undergone surgery without perioperative corticosteroids treatment. None of them displayed any features of hypocortisolism/adrenal crisis. Conclusions: CAI is rare (1.2%) in adults with PWS. Based on these results, we recommend against routinely prescribing corticosteroids stress-doses in adults with PWS. Funding: CZ foundation.

How COVID-19 Has Changed the Management of Glomerular Diseases.

A 26-year-old woman contacted our office asking for an urgent call back. She had a history of steroid-dependent and frequently relapsing minimal change disease, and calls like this usually meant her home dipsticks had turned positive. Instead, she reported that she had just tested positive for the

Perioperative care of congenital adrenal hyperplasia \u2013 a disparity of physician practices in Canada

BackgroundCongenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is the most common cause of primary adrenal insufficiency in children. Current guidelines recommend the use of perioperative stress dose (supraphysiologic) glucocorticoids for children with CAH undergoing anesthesia, although a perceived difference in practice patterns among Canadian pediatric subspecialists prompted an assessment of perioperative glucocorticoid administration.MethodsWe performed a cross-sectional survey of Canadian Pediatric Anesthesia Society (CPAS) and Canadian Pediatric Endocrine Group (CPEG) members via membership email lists to assess reported practice patterns to select clinical scenarios.ResultsResponses were collected from 49 anesthesiologists and 37 pediatric endocrinologists. Less than half of anesthesiologists reported they would provide stress dose corticosteroids for patients undergoing cystoscopy while a significant majority of pediatric endocrinologists reported they would recommend stress dose corticosteroid administration (45% vs 92% respectively, p < 0.0001). Twenty-one percent of anesthesiologists reported they would not provide stress dose corticosteroids for patients undergoing laparotomy. Pediatric endocrinologists reported they were more likely to refer to guidelines for management of stress dose steroids (84% vs 51%, p < 0.001), with many Canadian pediatric endocrinologists reporting to use institution specific guidelines.ConclusionsOur results demonstrate a clear difference in the reported approach to perioperative stress dose steroids between pediatric anesthesiologists and pediatric endocrinologists which may impact patient care. Further dialogue is required to address this apparent discrepancy in practice patterns and future research is needed to provide evidence-based practice recommendations.

Perioperative Pulmonary Medication Management.

Pulmonary conditions such as asthma and chronic obstructive pulmonary disease (COPD) are common conditions that warrant special consideration in the perioperative period. When these patients undergo surgical interventions, they have risk of complications such as bronchospasm, hypoxia, and even postoperative respiratory failure that warrant unplanned intensive care unit admission. Thus, clinicians must be familiar with pulmonary medication regimens that are critical for maintaining stable homeostasis of these chronic conditions. To discuss the medications most commonly used to treat pulmonary conditions and to describe strategies for handling these treatment regimens in the perioperative period. We conducted an online search of studies and review articles through PubMed and Medline that addressed pharmacology and perioperative management of pulmonary medications, with an emphasis on those treating patients with asthma or COPD. Long-term medications for pulmonary disease are used to slow the progression of these conditions and reduce the occurrence of acute exacerbations. As such, these medications should be continued in the perioperative period. If the medications include oral corticosteroids or high-dose inhaled corticosteroids, stress-dose corticosteroid supplementation may be warranted to avoid adrenal insufficiency. Inhaled medications can be delivered through the anesthetic circuit, and some agents may be used to treat exacerbations during surgery. Patients with chronic pulmonary conditions have risk of perioperative complications. Their pulmonary treatment regimens should be maintained in the perioperative period to reduce the risk of such complications.

Stress-Dose Corticosteroid Versus Placebo in Neonatal Cardiac Operations: A Randomized Controlled Trial

Corticosteroids can improve the hemodynamic status of neonates with postoperative low cardiac output syndrome after cardiac operations. This study compared a prophylactically administered stress-dose corticosteroid (SDC) regimen against placebo on inflammation, adrenocortical function, and hemodynamic outcome. Forty neonates undergoing elective open heart operations were randomized into two groups. The SDC group received perioperatively 2 mg/kg methylprednisolone, and 6 hours after the operation, a hydrocortisone infusion (0.2 mg/kg/h) was started with tapering doses for 5 days. Placebo was administered in a similar fashion. An adrenocorticotropic hormone stimulation test was performed after the therapy. The primary endpoint of the study was plasma concentration of interleukin (IL-6). Secondary clinical outcomes included plasma cortisol, IL-10, C-reactive protein, echocardiographic systemic ventricle contractility evaluated by the Velocity Vector Imaging program, the inotropic score, and time of delayed sternal closure. The IL-6 values of the SDC group were significantly lower postoperatively than in the placebo group. Significantly lower inotropic scores (p < 0.05), earlier sternal closure (p= 0.03), and less deterioration in the systemic ventricle mean delta strain values between the preoperative and the first postoperative assessment (p= 0.01) were detected for the SDC group. The SDC therapy did not suppress the hypothalamic-pituitary-adrenal axis more than placebo. The mean plasma cortisol level did not decline in the placebo group after the operation. The SDC regimen for 5 days postoperatively in neonates was safe and did not cause suppression of the hypothalamic-pituitary-adrenal axis. Furthermore, the open heart operation per se did not lead to adrenal insufficiency in neonates.

To use or not to use corticosteroids for pneumonia? A clinician’s perspective

The use of corticosteroids in the management of pneumonia is still a controversial issue. The physicians in daily clinical practice often use corticosteroids in patients with pneumonia for different reasons all over the world. As an example of real life is the frequent use of corticosteroids to treat patients with pneumonia due to H1N1 pandemic influenza in spite of WHO' statements that clearly discouraged this therapy. In fact, the literature up to august 2012 reported a total of 6,650 patients with pneumonia due to H1N1 virus infection (of whom 2,515 were ICU patients): corticosteroids were used with various dose regimen in 2404 patients (37.8%). The attitude of international guidelines on pneumonia in using steroids do not help the clinician to clearly choice when and how to treat pneumonia with steroids. However, stress doses of corticosteroids are suggested by some major guidelines on community-acquired pneumonia in case of severe episodes with sepsis. To date, there are 10 randomised controlled trials assessing the effectiveness of corticosteroids for community-acquired pneumonia globally involving 1090 participants. Most of the trials adopted stress doses of glucorticoids for 4-7 days. The evidence from these trials taken separately is weak due to limitations of the studies themselves, but a Cochrane review and a systematic review found benefit using prolonged low doses of glucocorticoids in severe community-acquired pneumonia. Moreover, such a strategy decreases vasopressor dependency and appears to be safe. Nevertheless, larger trials with more patients and clinically important end-points were claimed to provide robust evidence. Finally, infection surveillance is critical in patients treated with corticosteroids, and to prevent the rebound phenomenon, the drug should be weaned slowly.

46-Year-Old Man With Abdominal Pain and Hypotension

Resident in Internal Medicine, Mayo School of Graduate Medical Education, Mayo Clinic, Jacksonville, FL (O.A.W., D.F.S.); Adviser to residents and Consultant in Hospital Internal Medicine, Mayo Clinic, Jacksonville, FL (N.L.D.). A 46-year-old man with a history of type 2 diabetes, tetralogy of Fallot, and a bioprosthetic pulmonary valve replacement presented to the emergency department feeling generally unwell after eating a meal at a restaurant. The patient was in his usual state of health until starting dinner at the restaurant. The meal included cooked seafood, which consisted of different types of fish, shrimp, and scallops. A few minutes into his meal, he was overtaken by a sudden onset of severe back pain and cramping that radiated to his abdomen, mainly in the periumbilical region. He rated the pain as 8 of 10 on the severity scale. The pain was followed by progressively worsening dizziness and blurry vision. He also experienced intense palpitations, giving him the sensation of “wanting to pass out.” The patient had no known allergies to fish, seafood, or iodine. He had never experienced any of these symptoms before. None of his colleagues who ate with him had any similar symptoms. He had not recently traveled. On arrival at the emergency department, he became nauseated and vomited 6 times. He appeared to be moderately distressed. He was afebrile, his heart rate was 115 beats/min, and his blood pressure was 78/ 56 mm Hg. Physical examination yielded unremarkable findings except for erythema on his cheeks and mild wheezing on pulmonary examination. Laboratory tests, including complete blood cell count, metabolic profile, and liver function tests, revealed normal values except for a lactate level of 2.1 mmol/L (reference range, 0.6-2.3 mmol/L). Electrocardiography detected sinus tachycardia, and computed tomography of the abdomen with contrast medium revealed diffuse small-bowel wall thickening, edema, and mesenteric fluid with engorgement of the vasa recta. He was admitted to the hospital for further evaluation and treatment.

Cortisol Response To Low Dose Versus Standard Dose (Back-to-Back) Adrenocorticotrophic Stimulation Tests In Children and Adolescents With Thalassemia Major

Patients with thalassemia major(TM ), especially those with inadequate iron chelation, have high prevalence of endocrinopathies. Several studies reported a significant prevalence of subclinical “biochemical” adrenal insufficiency, ranging from 18–45%, in patients with thalassemia. This variability may be due to the different severity of TM, iron overload status, the test used for assessing adrenal function, and the cutoff value used to define subnormal cortisol response. The low dose (LD) 1-microg (ug) ACTH test follows the insulin tolerance test (ITT) has been shown to be more closely and more sensitive than the standard ACTH test in detecting more subtle insufficiency of the hypothalamic-pituitary-adrenal axis. Therefore the 1 ug ACTH test may be more appropriate for screening for secondary AI in TM patients. Measurements of serum dehydroepiandrosterone sulfate (DHEA-S) levels during LD simulation provide additional valuable information that improves the diagnostic accuracy of LDC in patients suspected to have central adrenal insufficiency (AI). The aim of this study was to compare cortisol and DHEA-S responses to LD and SD ACTH tests in patients with TM. Patients and Methods This cross-sectional controlled study was conducted at the Departments of Pediatrics and Hematology, Hamad Medical Center (HMC). 10 children and 13 adolescents (age 8 to 26 years ) were randomly recruited. They had been receiving blood transfusion at a regular basis every 4 wk. Iron chelation therapy was suboptimal in most of them. Patients were excluded if they had any other endocrine or systemic disease or drugs known to affect adrenal functions. 13 healthy children and adolescents with normal variant short stature served as controls. Serum cortisol and DHEA-S concentrations were determined in each subject before blood transfusion both in basal condition and after low dose (LD) (1 microgram) followed by standard dose (SD) (250 micrograms) respectively) with synthetic corticotrophin beta 1-24 ACTH (Synacthen Ciba). Normal controls were a group of 13 age and sex matched normal subjects. Results Using a peak total cortisol cutoff level of 550 nmol/L and increments of 200 ug above basal cortisol, AI was demonstrated in 8 patients after the LD ACTH and in 2 patients after SD ACTH test and in none of the controls. Using a peak total cortisol cutoff level of 420 nmol/L and increments of 200 ug above basal cortisol, AI was demonstrated in 5 patients after the LD ACTH and in 2 patients after SD ACTH test but none of controls. All patients with biochemical AI were asymptomatic with normal serum Na and K concentrations and no history suggestive of adrenal pathology. The peak cortisol concentrations in thalassemic patients with impaired adrenal function both after 1ug and 250 ug cosyntropin, ( 294 +/- 51 nmol/L and 307 +/- 58.6) were significantly lower than those with patients with normal ( 454 +/- 79.7 nmol/L and 546.1 +/- 92.2 nmol/L respectively) and controls (460.2 +/- 133.4 nmol/L and 554.3 +/- 165.8 nmol/L respectively). Adolescents but not children with TM had significantly lower peak cortisol concentration after SD cosyntropin test versus controls. Peak cortisol response to LD cosyntropin test was correlated significantly with peak cortisol response to SD in all patients (r = 0.83, p &lt; 0.0001). In adolescents with thalassemia DHEA-S levels before and after LD ACTH stimulation were significantly lower and the cortisol/DHEA-S ratios significantly higher than controls. In conclusion, the use of LD ACTH test diagnoses more adrenal abnormalities versus SD ACTH in thalassemic patients. The relatively high prevalence of AI in thalassemic adolescents necessitates that these patients have to be investigated for AI before major surgery and those with impaired cortisol secretion should receive stress doses of corticosteroids during the stressful event. Disclosures: No relevant conflicts of interest to declare.

Survival After Shock Requiring High-Dose Vasopressor Therapy

Some patients with hypotensive shock do not respond to usual doses of vasopressor therapy. Very little is known about outcomes after high-dose vasopressor therapy (HDV). We sought to characterize survival among patients with shock requiring HDV. We also evaluated the possible utility of stress-dose corticosteroid therapy in these patients. We conducted a retrospective study of patients with shock requiring HDV in the ICUs of five hospitals from 2005 through 2010. We defined HDV as receipt at any point of ≥ 1 μg/kg/min of norepinephrine equivalent (calculated by summing norepinephrine-equivalent infusion rates of all vasopressors). We report survival 90 days after hospital admission. We evaluated receipt of stress-dose corticosteroids, cause of shock, receipt of CPR, and withdrawal or withholding of life support therapy. We identified 443 patients meeting inclusion criteria. Seventy-six (17%) survived. Survival was similar (20%) among the 241 patients with septic shock. Among the 367 nonsurvivors, 254 (69%) experienced withholding/withdrawal of care, and 115 (31%) underwent CPR. Stress-dose corticosteroid therapy was associated with increased survival (P = .01). One in six patients with shock survived to 90 days after HDV. The majority of nonsurvivors died after withdrawal or withholding of life support therapy. A minority of patients underwent CPR. Additionally, stress-dose corticosteroid therapy appears reasonable in patients with shock requiring HDV.