Comparison of Metaraminol, Phenylephrine, and Norepinephrine Infusion for Prevention of Hypotension During Combined Spinal-Epidural Anaesthesia for Elective Caesarean Section: A Three-Arm, Randomized, Double-Blind, Non-Inferiority Trial.

BACKGROUND: A direct comparison of phenylephrine, metaraminol, and norepinephrine in preventing hypotension during spinal anaesthesia for elective caesarean section has never been made. PATIENTS AND METHODS: Seventy-five parturients scheduled for elective caesarean section were randomly assigned into the three groups. After spinal anaesthesia induction, patients received a bonus dose of vasopressor (norepinephrine 4ug, phenylephrine 50ug, or metaraminol 250ug) combined with continuous infusion (norepinephrine 8ug/mL, phenylephrine 100ug/mL, or metaraminol 500ug/mL) at a rate of 30 mL/h to prevent hypotension. The primary outcome was umbilical arterial (UA) pH and other intraoperative data were also recorded. RESULTS: The UA pH was 7.32±0.03 for metaraminol, 7.31±0.03 for phenylephrine, and 7.31±0.03 for norepinephrine. The 95% CI of MD was -0.011 to 0.026 comparing metaraminol with norepinephrine and 0.0181 to 0.0182 comparing phenylephrine with norepinephrine. Both lower bounds of the 95% CI of MD were above the predetermined lower boundary of clinical non-inferiority of -0.03, indicating both metaraminol and phenylephrine were non-inferior to norepinephrine. Moreover, the incidence of hypotension was lower in metaraminol compared with norepinephrine (P = 0.01). However, the incidence of hypertension was significantly lower in both phenylephrine and metaraminol compared with norepinephrine. CONCLUSION: Both metaraminol and phenylephrine were non-inferior to norepinephrine with respect to neonatal UA pH when used as a bolus and continuous infusion to prevent hypotension during combined spinal-epidural anaesthesia for elective caesarean section.

Effect of remimazolam induction on hemodynamics in patients undergoing valve replacement surgery: A randomized, double-blind, controlled trial.

BACKGROUND: The stability of hemodynamics during anesthesia induction in patients undergoing valve replacement surgery is particularly important. Remimazolam is a new type of benzodiazepine drug, with supposed advantages of rapid induction, rapid recovery, stable hemodynamics, and mild respiratory inhibition. AIM: To evaluate the effect of remimazolam anesthesia induction on hemodynamics in patients undergoing valve replacement surgery. METHODS: This randomized, double-blind, controlled trial enrolled consecutive patients undergoing mitral valve replacement (MVR)/aortic valve replacement (AVR)/double-valve replacement (DVR) surgery on cardiopulmonary bypass (CPB). The study was conducted according to the Consolidated Standards of Reporting Trials statement. Participants were randomly assigned to receive either remimazolam or propofol induction of 30 patients each. All patients, data collectors, and data analyzers were blinded to the group allocation. The primary outcomes were the fluctuations in hemodynamic parameters (the difference of maximum or minimum heart rate to baseline, ▲HR, the difference of maximum or minimum mean arterial pressure to baseline, ▲MAP), the occurrence of cardiovascular events (hypotension, severe bradycardia), and the cumulative norepinephrine doses used per patient, averaged per group during induction. The secondary outcomes were hemodynamic parameters (heart rate, HR, mean arterial pressure, MAP, bispectral index, BIS, plasma lactic acid, Lac, and blood glucose, Glu values). RESULTS: A total of 60 patients with heart valve replacement were included in the final analysis, with 30 patients in each group. The ▲MAP was significantly lower in the remimazolam group than in the propofol group during induction (p < .05). The incidences of hypotension and the cumulative norepinephrine doses used per patient, averaged per group during induction were significantly lower in the remimazolam group than in the propofol group (p < .05). CONCLUSION: Remimazolam may be safe and effective for induction and may as an alternative to propofol during anesthesia induction in patients undergoing valve replacement surgery.

Efficacy of bolus-dose epinephrine to manage hypotension in the prehospital setting.

PURPOSE: Hypotension in the Emergency Department (ED) and the prehospital setting has been associated with significant morbidity and mortality. Limited literature exists exploring the utilization of intravenous (IV) bolus-dose epinephrine (BDE) by Emergency Medical Services (EMS). METHODS: A retrospective review evaluated patients transported to an academic medical center who had received IV BDE by a single urban EMS system from 2016 to 2020. The primary outcome was to assess the influence IV BDE had on systolic blood pressure (SBP). Secondary objectives were to assess changes in heart rate (HR), the impact of dose variability on SBP, and the incidence of severe hypertension (SBP > 220 mmHg). RESULTS: A total of 55 patients who received 96 administrations of IV BDE were included in the analysis. The most common individual dose was 10 µg (76.0%) and 45.5% received multiple doses. The median weight-based dose of BDE was 0.14 µg/kg. A significant increase in SBP (median 14.0 mmHg) was noted among all patients following BDE administration compared with baseline (p < 0.001). No significant difference was found in HR following BDE compared with baseline (p = 0.375). Those that received a BDE dose >10 µg were noted to have a significantly greater rise in SBP than those that received 10 µg (30.0 mmHg vs. 11.0 mmHg; p = 0.022). Similarly, patients that received a dose ≥0.2 µg/kg had a significantly greater increase in SBP compared with those that received <0.2 µg/kg (30.0 mmHg vs. 10.0 mmHg; p = 0.048). There were no incidences of severe hypertension following therapy. CONCLUSION: The utilization of IV BDE in the prehospital setting for acute hypotension resulted in a significant rise in SBP. A dose-response relationship was noted both in terms of a flat-based dose and a weight-based dose, with higher doses yielding a greater change in SBP. Additional investigations are necessary to further explore the most appropriate dose of this agent in this setting and its influence, if any, on clinical outcomes.

Case Report: "Killer Bee" Swarm Attacks in French Guiana: The Importance of Prompt Care.

In French Guiana, a French overseas region partly located in the Amazon, "Africanized" bees, a hybrid species of Brazilian bees known as "killer bees," have been observed since 1975. Since then, several cases requiring long hospitalization times have been described, allowing for a better understanding of the physiopathological mechanisms of this particular envenomation. Here, we report on a series of 10 cases of patients simultaneously attacked by hundreds of killer bees and immediately treated by a prehospital medical team already on site. Between 75 and 650 stingers were removed per victim. The reference treatment for anaphylaxis using intramuscular injection of epinephrine, vascular filling, and oxygen therapy was administered to all patients without delay. A clinical description was provided, and biological tests were performed immediately after the envenomation. We therefore observe the existence of a two-phase, medically well-controlled systemic toxic reaction. Thus, all our patients left the hospital after 44 hours of monitoring with no complications or sequelae, despite levels of intoxication described as potentially fatal elsewhere in the literature.

Intranasal oxytocin has sympathoexcitatory effects on vascular tone in healthy males.

Oxytocin appears to be involved in the neuroendocrine regulation of sympathetic blood pressure (BP) homeostasis. In animals, intracerebral administration of oxytocin induces BP-relevant sympathetic activation. In humans, central nervous effects of oxytocin on BP regulation remain unclear. Intranasal administration supposedly delivers oligopeptides such as oxytocin directly to the brain. We investigated the effects of intranasal oxytocin on sympathetic vascular baroreflex function in humans using microneurographic techniques. In a balanced, double-blind crossover design, oxytocin or placebo was administered intranasally to 12 lean, healthy males (age 25 ± 4 yr). Muscle sympathetic nerve activity (MSNA) was assessed microneurographically before (presubstance), 30-45 min (postsubstance I), and 105-120 min (postsubstance II) after oxytocin administration. Baroreflex was challenged via graded infusions of vasoactive drugs, and correlation of BP with MSNA and heart rate (HR) defined baroreflex function. Experiments were conducted in the afternoon after a 5-h fasting period. After oxytocin, resting MSNA (burst rate and total activity) showed significant net increases from pre to postsubstance II compared with placebo [Δincrease = +4.3 ± 1.2 (oxytocin) vs. +2.2 ± 1.4 bursts/min (placebo), ANOVA; P < 0.05; total activity = 184 ± 11.5% (oxytocin) vs. 121 ± 14.3% (placebo), ANOVA; P = 0.01). This was combined with a small but significant net increase in resting diastolic BP, whereas systolic and mean arterial BP or HR as well as baroreflex sensitivity at vasoactive drug challenge were not altered. Intranasally administered oxytocin induced vasoconstrictory sympathoactivation in healthy male humans. The concomitant increase of diastolic BP was most likely attributable to increased vascular tone. This suggests oxytocin-mediated upward resetting of the vascular baroreflex set point at centers superordinate to the mere baroreflex-feedback loop.

Patient/parent administered epinephrine in acute anaphylaxis.

BACKGROUND: Among patients with a known peanut allergy, previous studies suggest low carrying rates of epinephrine auto-injectors (EAIs) and hesitancy to self-administer epinephrine upon anaphylaxis onset. Given the high prescription rates of epinephrine and prevalence of peanut allergies, it is important to identify rates of on-scene EAI use and affecting factors. METHODS: The electronic medical records of 217 patients-either with an ED diagnosis of peanut anaphylaxis or diagnosis of anaphylaxis with a known epinephrine prescription from 2010 through May 2020--were reviewed for physician notes and demographic factors. RESULTS: Epinephrine was administered on-scene by 25.3% of anaphylaxis patients. Of the 6 health care professionals identified, 100% administered epinephrine on-scene. Females (32.2%) were administered epinephrine on-scene more frequently than males (19.8%; p = 0.04). Rate of epinephrine administration increased from 2010 through 2019 (p = 0.005). CONCLUSION: This study selected for individuals diagnosed with anaphylaxis, meaning EAI use should have been observed nearly 100% of the time. An administration rate of 22.6% observed among individuals not identified as health care professionals suggests that the majority of patients prescribed epinephrine have not used their EAIs, even when presented an opportunity for application. The administration rate of 100% observed among health care professionals indicates that comfort with EAIs facilitates willingness to administer on-scene. EAIs can range up to $900 in expense, thus physicians should employ EAI training devices and other training strategies.

Cardiovascular effects of increasing dosages of norepinephrine in healthy isoflurane-anesthetized New Zealand White rabbits.

OBJECTIVE: To characterize the cardiovascular effects of increasing dosages of norepinephrine (NE) in healthy isoflurane-anesthetized rabbits. STUDY DESIGN: Prospective experimental study. ANIMALS: A total of nine female ovariohysterectomized New Zealand White rabbits weighing 3.4 ± 0.2 kg (mean ± standard deviation). METHODS: Rabbits were premedicated intramuscularly with buprenorphine (0.05 mg kg-1) and midazolam (0.5 mg kg-1). Anesthesia was induced with intravenous propofol and maintained with a 1.1 × minimum alveolar concentration of isoflurane for this species to induce hypotension. Rabbits were administered NE infusions at three doses: low, 0.1 µg kg-1 minute-1; medium, 0.5 µg kg-1 minute-1; and high doses, 1 µg kg-1 minute-1 for 10 minutes each in that order. Cardiovascular variables including heart rate (HR), cardiac output (CO) by lithium dilution technique and systolic (SAP), mean (MAP) and diastolic (DAP) invasive arterial blood pressures measured in the auricular artery were recorded at baseline, 10 minutes after the start of the infusion of each NE treatment and 10 minutes after NE was discontinued. A linear mixed model and a type III anova with Tukey's post hoc comparison was performed (p < 0.05). RESULTS: Significant increases in SAP (28% and 90%), MAP (27% and 90%) and DAP (33% and 97%) were measured with medium and high dose treatments, respectively (p < 0.001), with no changes in CO. HR decreased and stroke volume increased significantly with high dose treatment (by 17% and 15%, respectively; p < 0.05). No arrhythmias were noticed with NE treatments. CONCLUSIONS AND CLINICAL RELEVANCE: The infusion of NE at 0.5-1.0 µg kg-1 minute-1 is a potentially effective treatment for hypotension in healthy isoflurane-anesthetized New Zealand White rabbits.

The importance of the epinephrine provocation test for the hidden type-1 congenital long QT syndrome.

Congenital long QT syndrome (LQTS) is a genetic channelopathy associated with a high incidence of sudden cardiac death in children and young adults. QT interval prolongation is typically the primary finding on the electrocardiography (ECG) recordings, but a normal QT interval may be seen in as many as 40% of patients with LQTS due to incomplete penetrance. A normal QT interval on ECG in patients with LQTS is known as hidden LQTS. An epinephrine provocation test can help in the diagnosis of hidden LQTS. This case report describes the use of an epinephrine provocation test to diagnose hidden LQTS in 3 patients who had normal QT interval and corrected QT interval on ECG and a family history of sudden cardiac death.

Acute and chronic sympathomimetic effects of e-cigarette and tobacco cigarette smoking: role of nicotine and non-nicotine constituents.

Electronic cigarettes (ECs) and tobacco cigarettes (TCs) both release nicotine, a sympathomimetic drug. We hypothesized that baseline heart rate variability (HRV) and hemodynamics would be similar in chronic EC and TC smokers and that after acute EC use, changes in HRV and hemodynamics would be attributable to nicotine, not non-nicotine, constituents in EC aerosol. In 100 smokers, including 58 chronic EC users and 42 TC smokers, baseline HRV and hemodynamics [blood pressure (BP) and heart rate (HR)] were compared. To isolate the acute effects of nicotine vs. non-nicotine constituents in EC aerosol, we compared changes in HRV, BP, and HR in EC users after using an EC with nicotine (ECN), EC without nicotine (EC0), nicotine inhaler (NI), or sham vaping (control). Outcomes were also compared with TC smokers after smoking one TC. Baseline HRV and hemodynamics were not different in chronic EC users and TC smokers. In EC users, BP and HR, but not HRV outcomes, increased only after using the ECN, consistent with a nicotine effect on BP and HR. Similarly, in TC smokers, BP and HR but not HRV outcomes increased after smoking one TC. Despite a similar increase in nicotine, the hemodynamic increases were significantly greater after TC smokers smoked one TC compared with the increases after EC users used the ECN. In conclusion, chronic EC and TC smokers exhibit a similar pattern of baseline HRV. Acute increases in BP and HR in EC users are attributable to nicotine, not non-nicotine, constituents in EC aerosol. The greater acute pressor effects after TC compared with ECN may be attributable to non-nicotine, combusted constituents in TC smoke.NEW & NOTEWORTHY Chronic electronic cigarette (EC) users and tobacco cigarette (TC) smokers exhibit a similar level of sympathetic nerve activity as estimated by heart rate variability. Acute increases in blood pressure (BP) and heart rate in EC users are attribute to nicotine, not non-nicotine, constituents in EC aerosol. Acute TC smoking increased BP significantly more than acute EC use, despite similar increases in plasma nicotine, suggestive of additional adverse vascular effects attributable to combusted, non-nicotine constituents in TC smoke.

Effect of topical Phenylephrine on the upper eyelid crease position.

PURPOSE: To investigate the effect of Phenylephrine test on the upper eyelid crease position. MATERIAL AND METHODS: This study follows a prospective and analytical design and included patients with unilateral acquired involutional ptosis recruited between January 2015 and January 2018. In the Phenylephrine test, 1 drop of Phenylephrine 10% was instilled on the inferior fornix of the ptotic eye and the eyelid crease position was evaluated 10 min after. RESULTS: A total of 60 patients were included in the final sample. The mean Margin-to-reflex distance 1 (MRD1) of the ptotic eye was 2.1 ± 1.0 and 3.8 ± 0.6 mm before and 10 min after the instillation of Phenylephrine, respectively. The difference between the means was statistically significant (p < 0.001). Ninety-five per cent of the eyes had a positive Phenylephrine test result. Of this, 100% showed a decrease in the height of eyelid crease after the drop. There was a statistically significant decrease in the height of eyelid crease from 10.3 ± 2.5 to 7.8 ± 2.0 mm (p < 0.001). CONCLUSION: Phenylephrine test not only affects the eyelid position but also the eyelid crease height. We show a significative decrease in eyelid crease height to a symmetrical level with the contralateral lid in all patients that had a positive Phenylephrine test result. This effect is probably due to a posterior lamella shortening secondary to Müller's muscle contraction and suggests that the eyelid crease is not only determined by the projections of levator aponeurosis, but also by the entire force vector of the upper eyelid retractors.

Plasma dopamine concentrations following dopamine infusion to isoflurane-anesthetized New Zealand White rabbits.

OBJECTIVE: To determine the pharmacokinetics of dopamine following a short infusion in isoflurane-anesthetized rabbits. STUDY DESIGN: Prospective, descriptive pharmacokinetic study. ANIMALS: A group of six adult female New Zealand White rabbits weighing 4.4 ± 0.2 kg. METHODS: Rabbits were anesthetized with isoflurane in oxygen and maintained at 1.2 × minimum alveolar concentration of isoflurane (2.3% atmosphere). Dopamine (30 µg kg-1 minute-1) was infused for 10 minutes. Arterial blood was sampled prior, during and following the infusion at various intervals for 1 hour. RESULTS: A one-compartment model with baseline concentration best fitted the time-plasma dopamine concentration data. Estimated typical population value (interindividual variability) for volume of distribution and clearance were 10.3 (232%) L kg-1 and 9.9 (508%) L minute-1 kg-1, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: There was a large degree of interindividual variation in the disposition of dopamine. The large volume of distribution and high metabolic clearance rate reported for dopamine in this study likely explains the lack of clinical efficacy of dopamine in rabbits at doses up to 30 µg kg-1 minute-1.

Comparative Effectiveness of Topically Administered Tranexamic Acid Versus Topical Oxymetazoline Spray for Achieving Hemostasis in Epistaxis.

BACKGROUND: The use of tranexamic acid (TXA) has recently gained popularity as a treatment modality for epistaxis in the emergency department. Previous studies have compared topical TXA to nasal packing. However, topical TXA has not yet been compared with topical oxymetazoline in the treatment of epistaxis. OBJECTIVES: This study compares the efficacy of the intravenous formulation of TXA applied topically vs. the vasoconstrictor oxymetazoline applied topically in achieving hemostasis in patients presenting to the emergency department with anterior epistaxis. METHODS: In this prospective study, patients presenting to the emergency department with the chief complaint of epistaxis, and meeting inclusion criteria, were allocated into 2 treatment groups; topical oxymetazoline vs. topical application of the intravenous preparation of TXA. Patients were assessed for time to hemostasis in the emergency department as well as the occurrence of rebleeding within the next 48 h after discharge. RESULTS: Hemostasis was achieved in 14 (78%) of the 18 patients in the TXA group compared with 7 (35%) of the 20 patients in the oxymetazoline group. While there were occurrences of rebleeding in the emergency department before discharge and at 48 h in both groups, 11 patients in the TXA group had no recurrence of bleeding compared with 5 in the oxymetazoline group. CONCLUSION: This study demonstrated that the topical application of the intravenous preparation of TXA is more effective than topical oxymetazoline for achievement of hemostasis in anterior epistaxis. This has clinical significance toward preventing an avoidable need for escalation of treatment that could include applying nasal packing or cautery as well as preventing avoidable return emergency department visits. These outcomes would increase cost, potentially increase patient discomfort, and prolong emergency department throughput time.

Bayesian group sequential designs for phase III emergency medicine trials: a case study using the PARAMEDIC2 trial.

BACKGROUND: Phase III trials often require large sample sizes, leading to high costs and delays in clinical decision-making. Group sequential designs can improve trial efficiency by allowing for early stopping for efficacy and/or futility and thus may decrease the sample size, trial duration and associated costs. Bayesian approaches may offer additional benefits by incorporating previous information into the analyses and using decision criteria that are more practically relevant than those used in frequentist approaches. Frequentist group sequential designs have often been used for phase III studies, but the use of Bayesian group sequential designs is less common. The aim of this work was to explore how Bayesian group sequential designs could be constructed for phase III trials conducted in emergency medicine. METHODS: The PARAMEDIC2 trial was a phase III randomised controlled trial that compared the use of adrenaline to placebo in out-of-hospital cardiac arrest patients on 30-day survival rates. It used a frequentist group sequential design to allow early stopping for efficacy or harm. We constructed several alternative Bayesian group sequential designs and studied their operating characteristics via simulation. We then virtually re-executed the trial by applying the Bayesian designs to the PARAMEDIC2 data to demonstrate what might have happened if these designs had been used in practice. RESULTS: We produced three alternative Bayesian group sequential designs, each of which had greater than 90% power to detect the target treatment effect. A Bayesian design which performed interim analyses every 500 patients recruited produced the lowest average sample size. Using the alternative designs, the PARAMEDIC2 trial could have declared adrenaline superior for 30-day survival with approximately 1500 fewer patients. CONCLUSIONS: Using the PARAMEDIC2 trial as a case study, we demonstrated how Bayesian group sequential designs can be constructed for phase III emergency medicine trials. The Bayesian framework enabled us to obtain efficient designs using decision criteria based on the probability of benefit or harm. It also enabled us to incorporate information from previous studies on the treatment effect via the prior distributions. We recommend the wider use of Bayesian approaches in phase III clinical trials. TRIAL REGISTRATION: PARAMEDIC2 Trial registration ISRCTN, ISRCTN73485024. Registered 13 March 2014, http://www.isrctn.com/ISRCTN73485024.

Analysis of endogenous epinephrine and norepinephrine enantiomers in rat plasma and application to a stereoselective pharmacokinetics.

Epinephrine and norepinephrine are a class of chiral endogenous catecholamines, which are known as major neurotransmitters. This work described a new LC-MS/MS method coupled with pre-column derivatization, enabling the simultaneous enantiomeric separation of epinephrine and norepinephrine in rat plasma. After protein precipitation procedure, the samples were derivatized with (S)-N-(4-nitrophenoxycarbonyl) phenylalanine methoxyethyl ester, [(S)-NIFE]. The derivatives resolved with good baseline separation on an ACQUITY UPLC BEH C18 column (100 mm × 2.1 mm, 1.7 µm) with mobile phase composed of methanol with 0.2% formic acid in water at a flow rate of 0.2 mL/min. Analysis was performed by multiple reaction monitoring in positive ionization mode. The linear ranges were 1.0-500 ng/mL for epinephrine enantiomers and 1.5-750 ng/mL for norepinephrine enantiomers. The lower limits of quantification for epinephrine and norepinephrine enantiomers were 1.0 and 1.5 ng/mL, respectively. The intra-day and inter-day precision were all less than 10.7% and accuracy ranged from 96.0 to 101.5%. Recoveries for all the analytes were more than 80.3%. The proposed method was successfully applied to simultaneously determine endogenous epinephrine and norepinephrine enantiomers in rat plasma. l-epinephrine and l-norepinephrine were sensitively and accurately quantified while both the d-enantiomers were not detected. Additionally, epinephrine enantiomers were analyzed for stereoselective pharmacokinetics in rats after intravenous administration of racemic epinephrine for the first time. The pharmacokinetic results indicated that the disposition of epinephrine enantiomers was stereoselective and chiral inversion did not occur in rats.

Safety of Intradermal/Subcutaneous Lidocaine With Epinephrine Use in Dermatologic Surgery.

BACKGROUND: Recently, the safety of lidocaine plus epinephrine use in outpatient surgery has come under scrutiny despite its long history of use in outpatient dermatologic procedures and surgeries. OBJECTIVE: To assess the frequency of crash cart and other emergency interventions during Mohs micrographic surgery when lidocaine plus epinephrine is used as a local anesthetic and evaluate patient comorbidities associated with these events. MATERIALS AND METHODS: A retrospective chart review was conducted in an outpatient Mohs micrographic surgery clinic. RESULTS: One thousand one hundred twenty-seven Mohs cases were reviewed from the period of March 2015 to June 2016 with 864 meeting the inclusion criteria of patient weight, medical history, and amount of lidocaine administered recorded. No adverse events requiring emergency intervention with a crash cart or transfer to the emergency department occurred despite a patient population with advanced age and a wide range of comorbidities. CONCLUSION: No serious adverse events requiring emergency intervention were associated with lidocaine with epinephrine doses administered below the Food and Drug Administration recommended maximum. The authors did not find evidence from this study or after a literature search to support the requirement for a crash cart and other emergency equipment to be present during procedures.

Efficacy of Multimodal Analgesic Injections in Operatively Treated Ankle Fractures: A Randomized Controlled Trial.

BACKGROUND: Pain management following surgical treatment of an ankle fracture is an under-studied area of clinical practice. The present study evaluated the efficacy of a multimodal surgical-site injection as an adjunct to postoperative pain management in patients with an operatively treated, closed, rotational ankle fracture. METHODS: Patients indicated for operative fixation of a rotational ankle fracture were randomized to receive multimodal surgical-site injection (ropivacaine 200 mg, epinephrine 0.6 mg, and morphine 5 mg) or no injection (control). Visual analog scale (VAS) pain and opioid consumption data were collected every 4 hours until discharge from the hospital. Length of stay and discharge destination were recorded. Patients were sent automated text messages to report VAS pain and opioid usage during the first 2 weeks after discharge. RESULTS: One hundred patients (49 injection and 51 control) were enrolled. Demographic data were similar between the 2 groups. Mean VAS scores over the first 24 and 48 hours postoperatively were slightly lower in the injection group (42 ± 3 and 41 ± 3, respectively) compared with the control group (52 ± 3 and 50 ± 3, respectively; p = 0.01 and p < 0.01, respectively). The median opioid usage, in terms of morphine equivalent dose, was similar over the first 24 hours between the injection group (25.5; range, 0 to 74.7) and the control group (28.3; range, 2.5 to 91.0; p = 0.35). The median opioid usage from recovery room admission to discharge was also similar between the injection group (29.0; range, 0 to 85.3) and the control group (32.7; range, 4.3 to 215.0; p = 0.35). There were no differences in outpatient VAS scores or opioid consumption during the first 2 weeks postoperatively as assessed with use of automated text messaging. Median length of stay was 22.3 hours (range, 1.7 to 182.3 hours) for the injection group and 22.5 hours (range, 2.2 to 123.3 hours) for the control group (p = 0.71). The response rate for the post-discharge automated text messages was 85.1%. Complication rates were similar. CONCLUSIONS: The use of multimodal surgical-site injections in operatively treated rotational ankle fractures is associated with a reduction in immediate in-hospital pain scores that is statistically significant but below the minimal clinically important difference. LEVEL OF EVIDENCE: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

Comparative evaluation of a local anesthetic effect between lignocaine and lignocaine administered with epinephrine in healthy children.

Lignocaine a first amino amide-type local anesthetic, when combined or co-administered with epinephrine, a sympathomimetic amine, allows to administer larger doses for numbing, to decrease bleeding, and to make the numbing effect last longer. The study presented here focuses on measures to prove this activity in patients with abdominal surgery. Liposomal formulations of lignocaine and lignocaine plus epinephrine were prepared by a thin film evaporation method. This formulation was injected successfully as liposomal infusion. Thus prepared liposomes were found to be fit for drug delivery when evaluated as per physicochemical parameters. The smooth, even surfaced liposomes with PDI of 0.298 (p<0.05) were found to be efficient in delivering the drug when tested in-vitro (lignocaine as a single drug was at 93.78%, and from combined dosage lignocaine was at 96.29% with 94.62% of release of epinephrine). The randomized, controlled trial was conducted with a population of children that had undergone abdominal surgery and who were grouped into three groups depending upon the type of formulation they received. The three groups of subjects were first one receiving lignocaine liposomal infusion only; second one with lignocaine plus epinephrine liposomal infusion; the third group served as control and received a saline solution only. The serum Cortisol concentration was found to be the least in Group II when compared to Group I. Similarly, end point measurements such as the cool sensation, warm sensation, hot pain, and the sensory blockade test had indicated the superiority of combination of lignocaine with epinephrine in lowering the pain threshold. The result obtained from the above study has shown that epinephrine markedly enhances the local anesthetic activity of lignocaine.

Ephedrine-Induced Increases in Blood Pressure and Heart Rate Due to Suspected Cardiac Sympathetic Denervation Supersensitivity in a Patient with Parkinson's Disease Under Spinal Anesthesia.

BACKGROUND Denervation supersensitivity to sympathomimetic drugs has been noted in patients with Parkinson's disease (PD) whose cardiac sympathetic nerves are denervated. This phenomenon is not as well recognized as other complications of PD patients, but anesthesiologists should be aware of it because sympathomimetic drugs can sometimes be dangerous to these patients. CASE REPORT A 60-year-old woman was scheduled for total hip joint replacement under combined spinal-epidural anesthesia and sedation. She had been diagnosed as PD (stage 4 on the Hoehn and Yahr scale) with a history of orthostatic hypotension. Her ¹²³I-metaiodobenzylguanidine (MIBG) scintigraphy revealed marked reduction of ¹²³I-MIBG accumulation in the heart. In the operating room, we placed an epidural catheter through the Th12-L1 space, and spinal anesthesia (2.6 mL of 0.5% normobaric bupivacaine) was administered. During the surgery, we infused propofol at 100 mg·hr⁻¹ for sedation. When 4 mg of ephedrine was administered intravenously because of marked decrease in patient's blood pressure, we observed unexpectedly large increases in the systolic blood pressure, from 78 mmHg to 168 mmHg, and the heart rate increased from 52 to 84 beats per minute (bpm). This phenomenon recurred each time 4 mg of ephedrine was administered. CONCLUSIONS We report a case in which ephedrine induced unexpectedly large increases in blood pressure and heart rate in a patient who suffered from PD with severe cardiac sympathetic nerve denervation. We speculate that this phenomenon was caused by denervation supersensitivity of the patient's heart.