Hemodynamic effects of withholding vs. continuing angiotensin II receptor blockers on the day of prone positioning spinal surgery in elderly patients.

Introduction: The hemodynamic effects of withholding vs. continuing angiotensin II receptor blockers (ARBs) before surgery in elderly patients undergoing spinal surgery in a prone position during anesthesia induction to skin incision are still unknown. Methods: In this prospective study, 80 patients undergoing spinal surgery in a prone position with general anesthesia, aged 60-79 years, American Society of Anesthesiologists (ASA) II or III, were enrolled. Patients who had ARBs only in their preoperative medication list were randomly divided into two groups at a 1:1 ratio: In Group A, ARBs were continued on the morning of surgery, while in Group B, they were withhold. Norepinephrine was infused to maintain the blood pressure at the baseline level of ±20% during anesthesia induction in all patients. The primary outcome was the consumption of norepinephrine in each group from anesthesia induction to skin incision. The secondary outcomes include changes in invasive arterial blood pressure and heart rate, the fluid infusion volumes, the amounts of anesthetic drugs, and the total time from induction to skin incision. Results: There were no significant differences in the demographics, the fluid infusion volumes, the amounts of anesthetic drugs, the total time from induction to skin incision, and hemodynamics at different time points (p > 0.05), while significant differences were found in norepinephrine consumption between the two groups (p < 0.001). Compared with Group B, the consumption of norepinephrine increased significantly in Group A (93.3 ± 29.8 vs. 124.1 ± 38.7 µg, p = 0.000). In addition, the same trend was illustrated in the pumping rate of norepinephrine between Group B (0.04 ± 0.01 µg·kg-1·min-1) and Group A (0.06 ± 0.02 µg·kg-1·min-1) (p = 0.004). Conclusion: Our study conducted in elderly patients with hypotension undergoing prone spinal surgery demonstrated a greater pumping rate of norepinephrine during anesthesia induction in patients with ARBs continuing before surgery than those withholding, indicating that it was more difficult to maintain hemodynamic stability.Clinical Trial Registration: https://www.chictr.org.cn/showproj.html?proj=141081, ChiCTR2100053583.

Incidence and Pattern of Aminotransferase Elevation During Anti-Hypertensive Therapy With Angiotensin-II Receptor Blockers.

BACKGROUND: Angiotensin type II receptor blockers (ARBs) are the most widely used anti-hypertensive drugs. This study aimed to elucidate the likelihood and pattern of ARB-induced liver injury in a hospital-based cohort. METHODS: Data of patients receiving fimasartan (n = 5,543), candesartan (n = 6,406), valsartan (n = 6,040), and losartan (n = 9,126) were retrieved from the clinical data warehouse of two tertiary hospitals. Patients with alanine aminotransferase (ALT) levels > 5 times the upper normal limit were assessed according to the Roussel Uclaf Causality Assessment Method (RUCAM). RESULTS: A total of 27,115 patients were enrolled, including 14,630 (54.0%) men, with a mean age of 64.6 years (standard deviation, 13.6). During 31,717 person-years of ARB therapy, serum ALT levels > 120 IU/L were found in 558 (2.1%) person-years, and levels > 200 IU/L were found in 155 (0.6%) person-years. The incidence of ALT elevation > 120 IU/L per 106 cumulative defined daily doses was 6.6, 3.6, 3.9, and 4.0 in the fimasartan, candesartan, valsartan, and losartan groups, respectively (P = 0.002). An ALT level > 200 IU/L with RUCAM score ≥ 6 was found in 20 patients, suggesting probable drug-induced liver injury for 11 (0.2%) patients receiving fimasartan, five (0.1%) receiving candesartan, four (0.1%) receiving valsartan, and none receiving losartan (P < 0.001). CONCLUSION: Approximately 2% of patients receiving ARB therapy had significant ALT elevation (4.24/106 cumulative defined daily doses [cDDDs]), which was associated with probable ARB-related liver injury in 0.07% of patients (0.15/106 cDDDs). Elevation of ALT was more commonly associated with fimasartan than the other ARBs. Clinicians should be aware of the possibility of ARB-related ALT elevation in patients with unexplained chronic abnormal ALT.

Clinical Characterization of Patients With COVID-19 in Primary Care in Catalonia: Retrospective Observational Study.

BACKGROUND: The country of Spain has one of the highest incidences of COVID-19, with more than 1,000,000 cases as of the end of October 2020. Patients with a history of chronic conditions, obesity, and cancer are at greater risk from COVID-19; moreover, concerns surrounding the use of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin type II receptor blockers (ARBs) and its relationship to COVID-19 susceptibility have increased since the beginning of the pandemic. OBJECTIVE: The objectives of this study were to compare the characteristics of patients diagnosed with COVID-19 to those of patients without COVID-19 in primary care; to determine the risk factors associated with the outcome of mortality; and to determine the potential influence of certain medications, such as ACEIs and ARBs, on the mortality of patients with COVID-19. METHODS: An observational retrospective study of patients diagnosed with COVID-19 in the Catalan Central Region of Spain between March 1 and August 17, 2020, was conducted. The data were obtained from the Primary Care Services Information Technologies System of the Catalan Institute of Health in Barcelona, Spain. RESULTS: The study population included 348,596 patients (aged >15 years) registered in the Primary Care Services Information Technologies System of the Catalan Central Region. The mean age of the patients was 49.53 years (SD 19.42), and 31.17% of the patients were aged ≥60 years. 175,484/348,596 patients (50.34%) were women. A total of 23,844/348,596 patients (6.84%) in the population studied were diagnosed with COVID-19 during the study period, and the most common clinical conditions of these patients were hypertension (5267 patients, 22.1%) and obesity (5181 patients, 21.7%). Overall, 2680/348,596 patients in the study population (0.77%) died during the study period. The number of deaths among patients without COVID-19 was 1825/324,752 (0.56%; mean age 80.6 years, SD 13.3), while among patients diagnosed with COVID-19, the number of deaths was 855/23,844 (3.58%; mean age 83.0 years, SD 10.80) with an OR of 6.58 (95% CI 6.06-7.15). CONCLUSIONS: We observed that women were more likely to contract COVID-19 than men. In addition, our study did not show that hypertension, obesity, or being treated with ACEIs or ARBs was linked to an increase in mortality in patients with COVID-19. Age is the main factor associated with mortality in patients infected with SARS-CoV-2.

Antihypertensive Effects of Standardized Asafoetida: Effect on Hypertension Induced by Angiotensin II.

BACKGROUND: Asafoetida is an oleo-gum-resin obtained from the rhizome of Ferula assa-foetida plant that its effects on hypertension have been reported. This study examines the effect of aqueous extract of asafoetida on the cardiovascular parameters in acute hypertension induced by angiotensin II (AngII). MATERIALS AND METHODS: Thirty-six male rats were divided into six groups including Group 1: control; Group 2: AngII (50 ng/kg, intravenous); Group 3: losartan (Los; 10 mg/kg, i. p) + AngII; and Groups 4, 5, and 6 that received three doses of asafoetida (10, 30, and 60 mg/kg, i. p), separately. Los and extract were injected 30 min before hypertension induced by AngII. The femoral artery was cannulated and was connected to a pressure transducer, and cardiovascular parameters (systolic blood pressure [SBP], mean arterial pressure [MAP], and heart rate [HR]) were continuously recorded by a Power Lab system. The changes (Δ) of parameters were calculated and used for statistical analysis. RESULTS: AngII significantly increased the value of Δ SBP and Δ MAP compared to the control and significantly decreased Δ HR value. Injection of Los attenuated increased cardiovascular responses by AngII. Three doses of asafoetida ameliorated cardiovascular responses by AngII. Three doses of asafoetida decreased the Δ HR non significantly compared to AngII. CONCLUSION: Our results indicated that aqueous extract of asafoetida ameliorated cardiovascular responses in acute hypertension induced by AngII. This effect in a lower dose was more effective and comparable with Los. Therefore, a part of antihypertensive effect of asafoetida is mediated through inhibition of the AngII receptor type 1 receptor of AngII.

Influence of PD 123319 (AT2-Receptor Antagonist) on Catecholamine Secretion in the Perfused Rat Adrenal Medulla

BACKGROUND: The aim of this study was to examine whether PD 123319 (an angiotensin II type 2 [AT2] receptor antagonist) can influence the release of catecholamines (CA) from the perfused model of the rat adrenal medulla. METHODS: The adrenal gland was isolated by the modification of Wakade method, and perfused with normal Krebs-bicarbonate solution. The content of CA was measured using the fluorospectrophotometer. RESULTS: During perfusion of PD 123319 (range, 5 to 50 nM) into an adrenal vein for 90 minutes the CA secretory responses evoked by acetylcholine (ACh), high K+, 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP), and McN-A-343 was dose- and time-dependently inhibited. Furthermore, loading with PD 123319 for 90 minutes also markedly inhibited the CA secretory responses evoked by 4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoro-methyl-phenyl)-pyridine-5-carboxylate (Bay-K-8644), cyclopiazonic acid, veratridine, and angiotensin II (Ang II). PD 123319 did not affect basal CA output. Simultaneous perfusion of PD 123319 and CGP 42112 perfused into an adrenal vein for 90 minutes rather more potently inhibited the CA seretory responses evoked by Ach, high K+, DMPP, Bay-K-8644, veratridine, and Ang II compared to the inhibitory effect by PD123319-treated alone. CONCLUSIONS: Taken together, these results show that PD 123319 inhibits the CA secretion evoked by both cholinergic and Ang II receptor stimulation from the perfused rat adrenal medulla. This inhibitory effect of PD 123319 seems to be exerted by blocking the influx of both Na+ and Ca2+ through their voltage-dependent channels into the rat adrenomedullary chromaffin cells as well as by reducing the Ca2+ release from its cytoplasmic calcium store, which may be relevant to AT2 receptor blockade. Based on these present data, it is thought that PD 123319 has different activity from previously known AT2 antagonist activity in the perfused adrenal medulla, and that AT2 receptors may be involved in the rat adrenomedullary CA secretion.