Paracetamol 500mg / Phenylephrine 6.1mg tablets

BackgroundEphedrine, phenylephrine, and norepinephrine are commonly used to manage hypotension during the induction of anaesthesia. The objective of this study was to evaluate whether prophylactic administration of assumed equipotent doses of these vasopressors could maintain systolic arterial blood pressure (SAP) and heart rate (HR) within 80% of baseline for the first 5 min following induction of anaesthesia.MethodsThis randomised, double-blind, dose-controlled study was conducted at the Day Surgery Unit of Haugesund Hospital, Norway. One hundred and twenty-eight healthy women scheduled for gynaecological surgery were randomly allocated in a 1:1:1:1 ratio to receive prophylactic administration of ephedrine (0.1 mg/kg), phenylephrine (1 μg/kg), norepinephrine (0.1 mg/kg), or placebo (sodium chloride 9 mg/mL) at a volume of 0.1 mL/kg. Anaesthesia was induced using target-controlled infusion (TCI) of propofol and remifentanil. The initial 2.5 min constituted a sedation phase, after which the targets of propofol and remifentanil were increased, and the assigned vasopressor was administered. Beat-to-beat haemodynamic monitoring was performed using the LiDCOplus system. The primary outcome variables were the maximal decrease in SAP and HR within 5 min following bolus administration. Secondary outcome measures included changes in stroke volume (SV), cardiac output (CO), and systemic vascular resistance (SVR).ResultsThe absolute changes in SAP (mean ± standard deviation) following vasopressor administration were -27 ± 8.9 (ephedrine), -40 ± 11 (phenylephrine), -41 ± 13 (norepinephrine), and -42 ± 10 (placebo) mmHg. The differences (95% confidence interval [CI]) in the maximal SAP change between placebo and the vasopressors were as follows: ephedrine, -15 (-22, -9.9) mmHg; phenylephrine, -2.3 (-8.8, 4.2) mmHg; and norepinephrine, -1.7 (-8.3, 4.9) mmHg. Relative reductions in SAP from baseline to minimum values were -20% for ephedrine, -30% for phenylephrine, -30% for norepinephrine, and -32% for placebo. The absolute changes (median, interquartile range) in HR with ephedrine, phenylephrine, norepinephrine, and placebo were -10 (-6.2 to -18), -19 (-17 to -26), -23 (-20 to -33), and -15 (-9.5 to -21) bpm, respectively. Relative changes from baseline to minimum values in HR were -17% for ephedrine, -30% for phenylephrine, -37% for norepinephrine, and -22% for placebo. The differences in SV change between groups were small. CO was best preserved with ephedrine (-22% ± 11%), while phenylephrine and norepinephrine were associated with greater reductions (-38% ± 7.8% and -42% ± 9.8%, respectively). SVR increased most markedly in the norepinephrine group, followed by phenylephrine, with the smallest increase observed in the ephedrine group.ConclusionProphylactic administration of ephedrine effectively maintained SAP, HR, and CO within the first 5 min following bolus injection at induction with propofol and remifentanil. In contrast, bolus administration of norepinephrine and phenylephrine demonstrated a short duration of action, with SAP comparable to placebo at 5 min. Based on these findings, prophylactic administration of a bolus ephedrine is recommended, whereas prophylactic phenylephrine or norepinephrine injections may not be clinically preferable for bolus use in this context.Trial registrationClinicalTrials.gov identifier NCT03864094, March 6, 2019 This trial assessed circulatory responses to three different commonly used vasoactive support (vasopressor) drugs given as a single bolus together anesthetic induction propofol and remifentanil, and this in a cardiovascularly healthy adult surgical cohort. Results demonstrated that pharmacodynamic patterns with the three different test drugs, along with a no-prophylactic vasopressor comparitor. Findings showed a favorable profile for ephedrine compared to phenylephrine or noradrenaline if choosing to give a vasopressor in this way.

Abstract licence: CC BY-NC

IntroductionOndansetron, a selective 5-hydroxytryptamine 3 (5-HT3) receptor antagonist, has been proven to be effective in the prevention of spinal-induced hypotension for elective cesarean section.MethodsA total of 138 primigravida parturients scheduled for elective cesarean section were randomly assigned to three groups. Groups ONDA4 and ONDA8, respectively, received 4 and 8 mg of ondansetron in 100 mL normal saline, before spinal anesthesia with 1.7 mL ropivacaine 0.75% and 15 mcg of fentanyl, whereas the CONTROL group received an equal volume of normal saline. Noninvasive blood pressure and heart rate were recorded upon arrival, before and after spinal injection, and thereafter every minute for a time period of 10 minutes along with total doses of phenylephrine (mcg) or ephedrine (mg). Time required for the spinal anesthesia to achieve a sensory and motor block at the T4 level and Bromage 3 scale respectively, as well as to regress to the T7 level and a Bromage 1 scale were noted. Maternal nausea/vomiting or shivering, umbilical artery pH, and neonatal Apgar score at 1 and 5 min were also recorded.ResultsThere were no differences between groups in systolic, diastolic blood pressure, heart rate (p=0.355, p=0.550, p=0.474 respectively), doses of phenylephrine or ephedrine, (p=0.920, p=0.142 respectively), time for the block to reach T4 (p=0.889) and Bromage scale 3 (p=0.269), or to regress to T7 (p=0.273) and Bromage scale 1 (p=0.392), the incidence of nausea/vomiting (p=0.898/p=0.365), umbilical artery pH (p=0.739), neonatal Apgar score at 1 and 5 min (p=0.936 and p=0.907 respectively).ConclusionOur results showed no significant effect of two different doses of ondansetron, in preventing maternal hypotension, following spinal anesthesia with ropivacaine for cesarean section.

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Adrenal insufficiency (AI) is characterized by inadequate steroid hormone production and is frequently a consequence of hypopituitarism, which is also associated with increased risk of osteoporosis due to deficiencies in growth hormone, gonadotropins, and other pituitary hormones. Zoledronic acid (ZA), a widely used bisphosphonate, is associated with acute phase reaction (APR) that may trigger adrenal crisis in susceptible individuals. We describe two patients with hypopituitarism and osteoporosis who developed adrenal crisis shortly after their first ZA infusion, despite stable physiological steroid replacement and acetaminophen prophylaxis. One presented with hypotension and shock within 24 h, the other with hypotension, severe hyponatremia, and seizures at 48 h. Both recovered after high-dose glucocorticoids and were later switched to denosumab without complications. These cases highlight the potential for adrenal crisis in patients with central AI receiving ZA and suggest that standard prophylaxis may be insufficient. Alternative therapies and enhanced precautions may be warranted in this vulnerable population.

Abstract licence: CC BY