Risk factors, hematological and biochemical profile associated with colic in Delman horses in Gresik, Indonesia

Background: Horses are herd animals that have been domesticated in the last century. In several countries, an overview of risk factors and clinical evaluation in horses with colic has not been well‐described. This study aimed to evaluate risk factors and hematological profiles in horses associated with colic in Gresik, East Java, Indonesia. Methods: A cross-sectional study was performed during April - October 2019. A total of 115 horses were diagnosed based on physical examination, clinical symptoms, and rectal examination. A questionnaire was asked to the horse-owners to analyze the risk factors while the clinical examination was performed and blood samples were collected for pre-treatment and 14 days post-treatment. Hematological profile was evaluated from a whole blood sample. Serum cortisol, plasma epinephrine, and norepinephrine concentrations were also evaluated after separating the aliquots. Results: Of the 115 horses, 96 were diagnosed with colic. The horses with colic showed a significant association between cases with gender (p<0.021), breed (p<0.000), wheat bran feeding (p<0.015), concentrate feeding (p<0.003), anthelmintics administration (p<0.000), gastrointestinal parasites (p<0.000), dental diseases (p<0.024), previous exposure to colic (p<0.000), body condition score (p<0.000), and access to water per day (p<0.000). Based on whole blood and serum evaluation, there were ameliorated significantly on the hematological profile (p<0.01), serum cortisol (p<0.05), and plasma epinephrine (p<0.01) at 14 days post-treatment. Conclusion: This study has identified factors associated with colic in Delman horses. The study provides crucial information to investigate cases of colic and to contribute the development of healthcare strategies during treatment and clinical evaluation.

Application Effects of Remimazolam and on Elderly Patients Undergoing Hip Replacement

Objective To explore the anesthetic and analgesic effects of remimazolam and propofol in elderly patients undergoing hip replacement and their effects on respiratory and circulatory systems, stress and cognitive function. Methods 60 elderly patients undergoing elective hip replacement in the hospital were selected as the research subjects, and they were divided into the remimazolam group and the propofol group according to the admission sequence of patients. The remimazolam group was anesthetized with remimazolam, and the propofol group was anesthetized with propofol. The anesthesia-related indicators, perioperative pain degree [Visual Analogue Scale (VAS)], circulatory indicators [heart rate, mean arterial pressure (MAP)] before anesthesia (T0), immediately before laryngeal mask insertion (T1), at 5 min after laryngeal mask insertion (T2), at 30 min after laryngeal mask insertion (T3) and at 5 min after laryngeal mask removal (T4), stress response indicators (plasma epinephrine, norepinephrine, cortisol) before anesthesia induction and at 24 h and 72 h after surgery, cognitive function [Mini-Mental State Examination (MMSE)] and adverse reactions were compared between the two groups. Results Among the 60 enrolled patients, only 1 case was excluded due to withdrawal, thus 30 cases in the remimazolam group and 29 cases in the propofol group were included. There were statistically significant differences in the heart rate, MAP, plasma epinephrine, norepinephrine, cortisol and VAS score in the two groups from the aspects of interaction effect and time-point effect (P<0.05). The heart rate and MAP at T1, T2 and T3 in the two groups were significantly decreased compared with those at T0, but the heart rate and MAP in the remimazolam group at T1, T2 and T3 were significantly higher than those in the propofol group (P<0.05). There were no statistical differences in the anesthesia time, awakening time and extubation time between the remimazolam group and the propofol group (P>0.05). The levels of plasma epinephrine, norepinephrine and cortisol in the two groups were significantly higher at 24 h and 72 h after surgery than those before anesthesia induction, and the above levels were significantly lower in the remimazolam group than those in the propofol group (P<0.05). The VAS scores at each time point in the two groups were significantly reduced compared to before surgery, but there was no statistically significant difference between the two groups after surgery (P>0.05). The MMSE scores of the two groups were significantly lower at 1 d and 3 d after surgery compared with those before anesthesia induction, but the score in the remimazolam group was significantly higher than that in the propofol group (P<0.05). In addition, the incidence rates of adverse reactions were significantly lower in the remimazolam group compared to the propofol group (P<0.05). Conclusion Compared with propofol, remimazolam can achieve equivalent anesthetic and analgesic effects in elderly patients undergoing hip replacement. However, the latter one can significantly relieve respiratory and circulatory suppression, stress response and cognitive dysfunction, with good safety. Trial registration Clinical trial ethics committee of Hefei second people's Hospital：2021- scientific research-032 (September 6, 2021).

Risk factors and hematological profile associated with colic in Delman horses in Gresik, Indonesia

Background: Horses are herd animals that have been domesticated in the last century. In several countries, an overview of risk factors and clinical evaluation in horses with colic has not been well‐described. This study aimed to evaluate risk factors and hematological profiles in horses associated with colic in Gresik, East Java, Indonesia. Methods: A cross-sectional study was performed during April - October 2019. A total of 115 horses were diagnosed based on physical examination, clinical symptoms, and rectal examination. A questionnaire was asked to the horse-owners to analyze the risk factors while the clinical examination was performed and blood samples were collected for pre-treatment and 14 days post-treatment. Hematological profile was evaluated from a whole blood sample. Serum cortisol, plasma epinephrine, and norepinephrine concentrations were also evaluated after separating the aliquots. Results: Of the 115 horses, 96 were diagnosed with colic. The horses with colic showed a significant association between cases with gender (p<0.021), breed (p<0.000), wheat bran feeding (p<0.015), concentrate feeding (p<0.003), anthelmintics administration (p<0.000), gastrointestinal parasites (p<0.000), dental diseases (p<0.024), previous exposure to colic (p<0.000), body condition score (p<0.000), and access to water per day (p<0.000). Based on whole blood and serum evaluation, there were ameliorated significantly on the hematological profile (p<0.01), serum cortisol (p<0.05), and plasma epinephrine (p<0.01) at 14 days post-treatment. Conclusion: This study has identified factors associated with colic in Delman horses. The study provides crucial information to investigate cases of colic and to contribute the development of healthcare strategies during treatment and clinical evaluation.

Comparison of intraosseous and intravenous epinephrine administration during resuscitation of asphyxiated newborn lambs

ObjectiveIntraosseous access is recommended as a reasonable alternative for vascular access during newborn resuscitation if umbilical access is unavailable, but there are minimal reported data in newborns. We compared intraosseous with intravenous epinephrine administration during resuscitation of severely asphyxiated lambs at birth.MethodsNear-term lambs (139 days’ gestation) were instrumented antenatally for measurement of carotid and pulmonary blood flow and systemic blood pressure. Intrapartum asphyxia was induced by umbilical cord clamping until asystole. Resuscitation commenced with positive pressure ventilation followed by chest compressions and the lambs received either intraosseous or central intravenous epinephrine (10 μg/kg); epinephrine administration was repeated every 3 min until return of spontaneous circulation (ROSC). The lambs were maintained for 30 min after ROSC. Plasma epinephrine levels were measured before cord clamping, at end asphyxia, and at 3 and 15 min post-ROSC.ResultsROSC was successful in 7 of 9 intraosseous epinephrine lambs and in 10 of 12 intravenous epinephrine lambs. The time and number of epinephrine doses required to achieve ROSC were similar between the groups, as were the achieved plasma epinephrine levels. Lambs in both groups displayed a similar marked overshoot in systemic blood pressure and carotid blood flow after ROSC. Blood gas parameters improved more quickly in the intraosseous lambs in the first 3 min, but were otherwise similar over the 30 min after ROSC.ConclusionsIntraosseous epinephrine administration results in similar outcomes to intravenous epinephrine during resuscitation of asphyxiated newborn lambs. These findings support the inclusion of intraosseous access as a route for epinephrine administration in current guidelines.

Low Adrenomedullary Function Predicts Acute Illness in Infants with Classical Congenital Adrenal Hyperplasia

Context Youth with classical congenital adrenal hyperplasia (CAH) exhibit abnormal adrenomedullary function with decreased epinephrine levels noted in newborns and young infants. Little is known about how this relates to morbidity during the first year of life. Objective To study plasma epinephrine levels in infants with classical CAH and examine the clinical significance of epinephrine deficiency in the first year of life. Design Prospective cohort study. Setting Study participants were recruited from a pediatric tertiary care center. Patients or Other Participants 36 infants with classical CAH due to 21-hydroxylase deficiency and 27 age-matched unaffected controls with congenital hypothyroidism. Main Outcome Measures Plasma epinephrine levels (N=27), CYP21A2 genotype (N=15), and incidence of acute illnesses from birth to 1 year of age (N=28). Results Epinephrine levels in CAH infants independently predicted illness incidence in the first year of life (β=-0.018, R=-0.45, P=0.02) and were negatively correlated with 17-hydroxyprogesterone at diagnosis (R=-0.51, P=0.007). Infants with salt-wasting CAH exhibited lower epinephrine levels as newborns than simple-virilizing infants (P=0.02). CAH patients had lower epinephrine as newborns than controls (P=0.007) and showed decreases in epinephrine from birth to 1 year of age (P=0.04). Null genotype was associated with lower newborn epinephrine and more illness in the first year of life, compared to less severe mutation categories. Conclusions Lower epinephrine levels are associated with increased risk of illness among CAH infants. While not currently part of clinical standard of care, measuring epinephrine levels and assessing genotype may help predict acute illness in the first year of life.

Effect of a Larger Flush Volume on Bioavailability and Efficacy of Umbilical Venous Epinephrine during Neonatal Resuscitation in Ovine Asphyxial Arrest

The 7th edition of the Textbook ofNeonatal Resuscitation recommends administration of epinephrine via an umbilical venous catheter (UVC) inserted 2–4 cm below the skin, followed by a 0.5-mL to 1-mL flush for severe bradycardia despite effective ventilation and chest compressions (CC). This volume of flush may not be adequate to push epinephrine to the right atrium in the absence of intrinsic cardiac activity during CC. The objective of our study was to evaluate the effect of 1-mL and 2.5-mL flush volumes after UVC epinephrine administration on the incidence and time to achieve return of spontaneous circulation (ROSC) in a near-term ovine model of perinatal asphyxia induced cardiac arrest. After 5 min of asystole, lambs were resuscitated per Neonatal Resuscitation Program (NRP) guidelines. During resuscitation, lambs received epinephrine through a UVC followed by 1-mL or 2.5-mL normal saline flush. Hemodynamics and plasma epinephrine concentrations were monitored. Three out of seven (43%) and 12/15 (80%) lambs achieved ROSC after the first dose of epinephrine with 1-mL and 2.5-mL flush respectively (p = 0.08). Median time to ROSC and cumulative epinephrine dose required were not different. Plasma epinephrine concentrations at 1 min after epinephrine administration were not different. From our pilot study, higher flush volume after first dose of epinephrine may be of benefit during neonatal resuscitation. More translational and clinical trials are needed.

Epinephrine to the Rescue: Identifying the Offending Side in Bilateral (B/L) Macronodular Adrenal Hyperplasia (BMAH) With Cushing Syndrome (CS) and Hyperaldosteronism

Management of ACTH-independent CS in the setting of B/L adrenal masses can be challenging. We present a patient with concomitant cortisol and aldosterone hypersecretion and B/L adrenal masses who was treated with unilateral adrenalectomy (UA) based on simultaneous B/L adrenal vein sampling (AVS) results normalized to plasma epinephrine levels, to correct for flow and dilution. A 60-year-old lady presented for evaluation of incidentally discovered B/L adrenal masses. CT abdomen with contrast revealed B/L lobulated adrenal glands measuring 3.4 x 5.5 x 4.1 cm on the right and 3.8 x 4.2 x 2 cm on the left (pre contrast density of 37 and 44 Hounsfield Units respectively). She had a recent diagnosis of HTN and prediabetes. She reported fatigue, easy bruising, and muscle weakness. Family history was notable for a sister with CS and B/L adrenal masses who was successfully treated with UA. On physical examination her BP was 160/94 mm Hg and she did not have an obvious cushingoid appearance. Laboratory testing included an elevated AM serum cortisol level of 16.6 mcg/dL following 1 mg of dexamethasone given at 11 pm the previous night. ACTH was &lt;1.0 pg/mL consistent with ACTH-independent CS. She had a serum aldosterone level of 26.6 ng/dL(4.0 - 31.0 ng/dL),simultaneous plasma renin activity of 0.5 ng/ml/hr (0.5–4 ng/ml/hr) and serum potassium level of 4.4 mmol/l. She underwent B/L simultaneous AVS. Given concomitant hyperaldosteronism, plasma epinephrine levels were measured to determine successful catheter placement and to correct for flow and dilution between the adrenal veins. Right adrenal vein to peripheral vein cortisol ratio was 9.27 (&gt; 6.5) consistent with cortisol hypersecretion. The right to left cortisol ratio was 2.3 (&gt;/= 2.3), consistent with right sided predominance. Right to left ratio of the epinephrine corrected cortisol level was 2.7. She underwent right adrenalectomy, and pathology showed macronodular adrenal hyperplasia. Postoperatively, she had resolution of HTN and normalization of 24 hour urine free cortisol. UA is increasingly becoming recognized as a successful treatment for BMAH due to lower risk of adrenal crisis when compared to B/L adrenalectomy. In a recent publication, remission from CS was seen in 94.4 % of patients with BMAH following UA, with recurrence in 19% of patients. The mean time to recurrence was 5 years. We utilized cutoff values that were previously reported for cortisol lateralization in interpreting AVS. Our patient attained remission of CS 9 months post UA. Epinephrine levels were not significantly different between the adrenal veins, possibly due to simultaneous AVS, so we were also able to calculate epinephrine corrected cortisol ratios. Simultaneous B/L AVS with epinephrine to localize autonomous hypercortisolism in the setting of concomitant hyperaldosteronism can be beneficial in guiding surgical management of patients.

Randomised trial of epinephrine dose and flush volume in term newborn lambs

ObjectivesNeonatal resuscitation guidelines recommend 0.5–1 mL saline flush following 0.01–0.03 mg/kg of epinephrine via low umbilical venous catheter for persistent bradycardia despite effective positive pressure ventilation (PPV) and chest compressions (CC). We evaluated the effects of 1 mL vs 3 mL/kg flush volumes and 0.01 vs 0.03 mg/kg doses on return of spontaneous circulation (ROSC) and epinephrine pharmacokinetics in lambs with cardiac arrest.DesignForty term lambs in cardiac arrest were randomised to receive 0.01 or 0.03 mg/kg epinephrine followed by 1 mL or 3 mL/kg flush after effective PPV and CC. Epinephrine (with 1 mL flush) was repeated every 3 min until ROSC or until 20 min. Haemodynamics, blood gases and plasma epinephrine concentrations were monitored.ResultsTen lambs had ROSC before epinephrine administration and 2 died during instrumentation. Among 28 lambs that received epinephrine, 2/6 in 0.01 mg/kg-1 mL flush, 3/6 in 0.01 mg/kg-3 mL/kg flush, 5/7 in 0.03 mg/kg-1 mL flush and 9/9 in 0.03 mg/kg-3 mL/kg flush achieved ROSC (p=0.02). ROSC was five times faster with 0.03 mg/kg epinephrine compared with 0.01 mg/kg (adjusted HR (95% CI) 5.08 (1.7 to 15.25)) and three times faster with 3 mL/kg flush compared with 1 mL flush (3.5 (1.27 to 9.71)). Plasma epinephrine concentrations were higher with 0.01 mg/kg-3 mL/kg flush (adjusted geometric mean ratio 6.0 (1.4 to 25.7)), 0.03 mg/kg-1 mL flush (11.3 (2.1 to 60.3)) and 0.03 mg/kg-3 mL/kg flush (11.0 (2.2 to 55.3)) compared with 0.01 mg/kg-1 mL flush.Conclusions0.03 mg/kg epinephrine dose with 3 mL/kg flush volume is associated with the highest ROSC rate, increases peak plasma epinephrine concentrations and hastens time to ROSC. Clinical trials evaluating optimal epinephrine dose and flush volume are warranted.

Plasma Epinephrine Contributes to the Development of Experimental Hypoglycemia-Associated Autonomic Failure

Background Recurrent hypoglycemia blunts counter-regulatory responses to subsequent hypoglycemic episodes, a syndrome known as hypoglycemia-associated autonomic failure (HAAF). Since adrenergic receptor blockade has been reported to prevent HAAF, we investigated whether the hypoglycemia-associated rise in plasma epinephrine contributes to pathophysiology and reported interindividual differences in susceptibility to HAAF. Methods To assess the role of hypoglycemia-associated epinephrine responses in the susceptibility to HAAF, 24 adult nondiabetic subjects underwent two 2-hour hyperinsulinemic hypoglycemic clamp studies (nadir 54 mg/dL; 0-2 hours and 4-6 hours) on Day 1, followed by a third identical clamp on Day 2. We challenged an additional 7 subjects with two 2-hour infusions of epinephrine (0.03 μg/kg/min; 0-2 hours and 4-6 hours) vs saline on Day 1 followed by a 200-minute stepped hypoglycemic clamp (90, 80, 70, and 60 mg/dL) on Day 2. Results Thirteen out of 24 subjects developed HAAF, defined by ≥20% reduction in average epinephrine levels during the final 30 minutes of the third compared with the first hypoglycemic episode (P &lt; 0.001). Average epinephrine levels during the final 30 minutes of the first hypoglycemic episode were 2.3 times higher in subjects who developed HAAF compared with those who did not (P = 0.006). Compared to saline, epinephrine infusion on Day 1 reduced the epinephrine responses by 27% at the 70 and 60 mg/dL glucose steps combined (P = 0.04), with a parallel reduction in hypoglycemic symptoms (P = 0.03) on Day 2. Conclusions Increases in plasma epinephrine reproduce key features of HAAF in nondiabetic subjects. Marked interindividual variability in epinephrine responses to hypoglycemia may explain an individual’s susceptibility to developing HAAF.

Possible effect of epinephrine in minimizing COVID-19 severity: a review

Objective Coronavirus disease 2019 (COVID-19) shows a wide range of severity, ranging from an asymptomatic presentation to a severe illness requiring intensive care unit admission. Identification of a strategy to manage the severity of this disease will not only help to reduce its case fatality but also help to remove some of the burden from the already overwhelmed health care systems. While successful management of symptoms in general is important, identifying measures to modify the severity of the illness is a key factor in the fight against this pandemic. Methods This paper presents a short literature review to suggest a new treatment modality for COVID-19. Results COVID-19 is less severe and rarely fatal in children than in adults, which could be caused by greater fluctuations of plasma epinephrine in children. Our literature survey endorses this hypothesis according to both the epidemiological and immunological findings. Conclusion Application of epinephrine pulses with a specific amplitude may be considered an intervention to minimize the severity of COVID-19.