Evaluation of the early use of norepinephrine in major abdominal surgery on medical and surgical postoperative complications: study protocol for a randomised controlled trial (EPON STUDY).

BACKGROUND: Post-induction anaesthesia often promotes intraoperative hypotension (IOH) that can worsen postoperative outcomes. This study aims to assess the benefit of norepinephrine versus ephedrine at the induction of anaesthesia to prevent postoperative complications following major abdominal surgery by preventing IOH. METHODS AND ANALYSIS: The EPON STUDY is a prospective single-centre randomised controlled trial with the planned inclusion of 500 patients scheduled for major abdominal surgery at the Amiens University Hospital. The inclusion criteria are patients aged over 50 years weighing more than 50 kg with an American Society of Anesthesiologists physical status score of ≥2 undergoing major abdominal surgery under general anaesthesia. Patients are allocated either to the intervention group (n=250) or the standard group (n=250). In the intervention group, the prevention of post-induction IOH is performed with norepinephrine (dilution to 0.016 mg/mL) using an electric syringe pump at a rate of 0.48 mg/h (30 mL/h) from the start of anaesthesia and then titrated to achieve the haemodynamic target. In the control group, the prevention of post-induction IOH is performed with manual titration of ephedrine, with a maximal dose of 30 mg, followed by perfusion with norepinephrine. In both groups, the haemodynamic target to maintain is a mean arterial pressure (MAP) of 65 mm Hg or 70 mm Hg for patients with a medical history of hypertension. An intention-to-treat analysis will be performed. The primary outcome is the Clavien-Dindo score assessed up to 30 days postoperatively. The secondary endpoints are the length of hospital stay and length of stay in an intensive care unit/postoperative care unit; postoperative renal function; postoperative cardiovascular, respiratory, neurological, haematological and infectious complications at 1 month; and volume of intraoperative vascular filling and mortality at 1 month. ETHICS AND DISSEMINATION: Ethical approval was obtained from the committee of protection of the persons of Ile de France in May 2021 (number 21 05 41). The authors will be involved in disseminating the research findings (through attending conferences and co-authoring papers). The results of the study will be disseminated via peer-reviewed publications and presentations at national and international conferences. TRIAL REGISTRATION NUMBER: NCT05276596.

A Pharmacokinetic Study of Ephedrine and Pseudoephedrine after Oral Administration of Ojeok-San by Validated LC-MS/MS Method in Human Plasma.

A sensitive and reproducible liquid chromatography-tandem mass spectrometry (LC-MS/MS) system was developed and fully validated for the simultaneous determination of ephedrine and pseudoephedrine in human plasma after oral administration of the herbal prescription Ojeok-san (OJS); 2-phenylethylamine was used as the internal standard (IS). Both compounds presented a linear calibration curve (r2 ≥ 0.99) over a concentration range of 0.2-50 ng/mL. The developed method was fully validated in terms of selectivity, lower limit of quantitation, precision, accuracy, recovery, matrix effect, and stability, according to the regulatory guidelines from the U.S. Food and Drug Administration and the Korea Ministry of Food and Drug Safety. This validated method was successfully applied for the pharmacokinetic assessment of ephedrine and pseudoephedrine in 20 healthy Korean volunteers administered OJS.

Therapeutic appraisal of ephedrine against rheumatoid arthritis: A new indication.

Ephedra, natural flora has been used traditionally to treat rheumatism since decades. The scientific evidence of anti-rheumatic effect of this plant has also been reported. But the anti-rheumatic activity of major constituent of this plant (ephedrine) has not been evaluated. Based on this, the current study was aimed to assess anti-arthritic activity of ephedrine by using in vitro and in vivo approaches. Correspondingly, enzyme linked immunosorbent assay was performed for the estimation of prostaglandins E2 (PGE2) and tumor necrosis factor-α (TNF-α) in serum of formaldehyde-induced arthritic animals. The results elaborated significant reduction in albumin denaturation and remarkable progress on stabilization of red blood cells outer membrane at higher concentration during in vitro experiments. The ephedrine (40mg/kg) revealed noteworthy (p<0.001) inhibition in paw swelling in animals intoxicated with albumin as well as formaldehyde as compared to animals of control group by in vivo results. In this assay, ephedrine (20 & 40 mg/kg orally) significantly suppressed the level of these inflammatory markers (PGE2 & TNF-α). Ephedrine exhibited anti-arthritic effect by decreasing pro-inflammatory cytokines (PGE2 & TNF-α). This experimental work pharmacologically supports the use of ephedrine as anti-rheumatic drug but limited to evaluate in immunological arthritic model.

Ephedrine pretreatment for nasotracheal intubation-related epistaxis in maxillofacial surgery with sufficient lubrication: A randomized clinical trial.

WHAT IS KNOWN AND OBJECTIVE: Prior to nasotracheal intubation (NTI), topical nasal vasoconstrictors are used to prevent NTI-related epistaxis (NTIRE). Since we learned that there is no significant increase in NTIRE among hypertensive patients undergoing NTI with adequate lubrication but without vasoconstrictors, we initiated this randomized controlled study to assess the necessity of vasoconstrictor use in reducing NTIRE. METHODS: Patients with the American Society of Anesthesiologists Physical Status Classification 1 and normal coagulation function, planned to undergo maxillofacial surgery with NTI were enrolled. Patients were randomly (1:1) assigned to each of the treatment groups: nasal treatment using pure oxybuprocaine gel with adequate lubrication (group G) or 1% ephedrine in addition to oxybuprocaine gel with adequate lubrication (group EG). In addition, the incidence and severity of NTIRE and intubation adjustments were studied. RESULTS: A total of 844 patients, 429 and 415 (groups G and EG, respectively), were included in the analysis. No significant differences were observed in the NTIRE incidence rates in groups G (28%) and EG (27%; p = 0.75, relative risk [RR] = 0.95, 95% confidence interval [CI] 0.70-1.29). No significant differences in the NTIRE incidence rates between the two nostrils were observed in both groups (group G: left, 27.9% vs. right, 28% [p = 0.98, RR = 1.01, 95% CI 0.67-1.51]; group EG: left, 25.8% vs. right, 27.9% [p = 0.63, RR = 1.12, 95% CI 0.72-1.73]. No significant difference was observed in the severity of NTIRE (p = 0.74). In case of difficult advancement of the endotracheal tube, NTIRE incidence was 71% vs. 12% with smooth intubation (p < 0.01, RR = 18.33, 95% CI 12.55-26.77). WHAT IS NEW AND CONCLUSION: Well-lubricated nasotracheal intubation does not require pretreatment with ephedrine to reduce NTIRE.

The effect of epinephrine for the treatment of spinal-hypotension: comparison with norepinephrine and phenylephrine, clinical trial / O efeito de epinefrina, norepinefrina e fenilefrina no tratamento da hipotensão pós-raquianestesia: estudo clínico comparativo

Abstract Background and objectives: Limited data are present on safety and efficiency of epinephrine for the prophylaxis and treatment of spinal-hypotension. This study was conducted to compare the effect of epinephrine with norepinephrine and phenylephrine on the treatment of spinal-hypotension and ephedrine requirement during cesarean delivery. Methods: One hundred and sixty parturients with uncomplicated pregnancies undergoing elective cesarean delivery under spinal anesthesia were recruited. They were allocated randomly to receive norepinephrine 5 µg.mL−1 (n = 40), epinephrine 5 µg.mL−1 (n = 40), phenylephrine 100 µg.mL−1 (n = 40) or 0.9% saline infusions (n = 40) immediately after induction of spinal anesthesia. Whenever systolic blood pressure drops to less than 80% of baseline, 5 mg of intravenous ephedrine was administered as rescue vasopressor. The incidence of hypotension, total number of hypotension episodes, the number of patients requiring ephedrine, the mean amount of ephedrine consumption and side effects were recorded. Results: There was no statistically significant difference in incidence of maternal hypotension between groups. The number of patients requiring ephedrine was significantly greater in group saline than in group phenylephrine (p< 0.001). However, it was similar between phenylephrine, norepinephrine, and epinephrine groups. The mean ephedrine consumption was significantly higher in group saline than in norepinephrine, epinephrine, phenylephrine groups (p= 0.001). Conclusion: There is no statistically significant difference in incidence of hypotension and ephedrine consumption during spinal anesthesia for cesarean delivery with the use of epinephrine when compared to norepinephrine or phenylephrine. Epinephrine can be considered an alternative agent for management of spinal hypotension.

Resumo Justificativa e objetivos: Existem dados limitados sobre segurança e eficiência da epinefrina na profilaxia e tratamento da hipotensão arterial associada à raquianestesia. O presente estudo foi realizado para comparar o efeito da epinefrina com norepinefrina e fenilefrina no tratamento da hipotensão após raquianestesia e necessidade de efedrina durante o parto cesáreo. Método: Foram recrutadas 160 parturientes com gestações não complicadas, submetidas a cesariana eletiva sob raquianestesia. Elas foram alocadas aleatoriamente para receber norepinefrina 5 µg.mL-1 (n = 40), epinefrina 5 µg.mL-1 (n = 40), fenilefrina 100 µg.mL-1 (n = 40) ou infusão de solução fisiológica NaCl a 0,9% (n = 40) imediatamente após a indução da raquianestesia. Sempre que houvesse redução da pressão arterial sistólica para valor inferior a 80% da linha de base, 5 mg de efedrina iv eram administrados como vasopressor de resgate. A incidência de hipotensão, o número total de episódios de hipotensão, o número de pacientes que necessitaram de efedrina, o consumo médio de efedrina e os efeitos colaterais foram registrados. Resultados: Não houve diferença estatisticamente significante na incidência de hipotensão materna entre os grupos. O número de pacientes que necessitaram de efedrina foi significantemente maior no grupo solução fisiológica do que no grupo fenilefrina (p< 0,001). No entanto, foi semelhante entre os grupos fenilefrina, norepinefrina e epinefrina. O consumo médio de efedrina foi significantemente maior no grupo solução fisiológica do que nos grupos norepinefrina, epinefrina e fenilefrina (p = 0,001). Conclusão: Não houve diferença estatisticamente significante na incidência de hipotensão e consumo de efedrina durante raquianestesia para parto cesáreo com uso de epinefrina quando comparada à norepinefrina ou fenilefrina. A epinefrina pode ser considerada como agente alternativo para o tratamento da hipotensão após raquianestesia.

[The effect of epinephrine for the treatment of spinal-hypotension: comparison with norepinephrine and phenylephrine, clinical trial]. / O efeito de epinefrina, norepinefrina e fenilefrina no tratamento da hipotensão pós­raquianestesia: estudo clínico comparativo.

BACKGROUND AND OBJECTIVES: Limited data are present on safety and efficiency of epinephrine for the prophylaxis and treatment of spinal-hypotension. This study was conducted to compare the effect of epinephrine with norepinephrine and phenylephrine on the treatment of spinal-hypotension and ephedrine requirement during cesarean delivery. METHODS: One hundred and sixty parturients with uncomplicated pregnancies undergoing elective cesarean delivery under spinal anesthesia were recruited. They were allocated randomly to receive norepinephrine 5 µg.mL-1 (n=40), epinephrine 5 µg.mL-1 (n=40), phenylephrine 100 µg.mL-1 (n=40) or 0.9% saline infusions (n=40) immediately after induction of spinal anesthesia. Whenever systolic blood pressure drops to less than 80% of baseline, 5 mg of iv ephedrine was administered as rescue vasopressor. The incidence of hypotension, total number of hypotension episodes, the number of patients requiring ephedrine, the mean amount of ephedrine consumption and side effects were recorded. RESULTS: There was no statistically significant difference in incidence of maternal hypotension between groups. The number of patients requiring ephedrine was significantly greater in group saline than in group phenylephrine (p <0.001). However, it was similar between phenylephrine, norepinephrine, and epinephrine groups. The mean ephedrine consumption was significantly higher in group saline than in norepinephrine, epinephrine, phenylephrine groups (p=0.001). CONCLUSION: There is no statistically significant difference in incidence of hypotension and ephedrine consumption during spinal anesthesia for cesarean delivery with the use of epinephrine when compared to norepinephrine or phenylephrine. Epinephrine can be considered as an alternative agent for management of spinal hypotension.

The efficacy of intramuscular ephedrine in preventing hemodynamic perturbations in patients with spinal anesthesia and dexmedetomidine sedation.

Dexmedetomidine is used for sedation during spinal anesthesia. The sympatholytic effect of dexmedetomidine may exacerbate hypotension and bradycardia with spinal anesthesia. This study investigated the effects of prophylactic intramuscular injection of ephedrine in preventing hypotension and bradycardia occurring through combined use of spinal anesthesia and dexmedetomidine. One hundred sixteen patients scheduled for lower extremity orthopedic surgery were randomized into two groups receiving either ephedrine 20 mg intramuscularly or equivalent amount of 0.9% NaCl, both with dexmedetomidine and spinal anesthesia. The primary endpoint was the incidence of hemodynamic perturbations (hypotension or bradycardia event). The secondary endpoint was a rescue doses of ephedrine and atropine. The incidence of hemodynamic perturbations was significantly lower in the ephedrine group compared with to the saline group (26.3% versus 55.9%, p = 0.001). The rescue doses of atropine (0.09 ± 0.21 versus 0.28 ± 0.41, p = 0.001) and ephedrine (1.04 ± 2.89 versus 2.03 ± 3.25, p = 0.007) were also significantly lower in the ephedrine group. There was no differences in number of patients with hypertensive (7.0% versus 11.9%, p = 0.375) or tachycardia (1.8% versus 3.4% p = 0.581) episodes. The use of ephedrine intramuscular injections may be a safe and efficacious option in preventing hemodynamic perturbations in patients who received spinal anesthesia and sedation using dexmedetomidine.

Respuesta clínica y neurofisiológica a la efedrina en un paciente con síndrome miasténico congénito de canal lento / Clinical and neurophysiological response to ephedrine in a patient affected with slow-channel congenital myasthenic syndrome

INTRODUCCIÓN: El síndrome miasténico congénito de canal lento, o síndrome de canales lentos, es un trastorno neuromuscular progresivo hereditario, autosómico dominante, causado por una activación anormal de los receptores de la acetilcolina en la unión neuromuscular. La alteración histopatológica característica es la degeneración selectiva de la placa terminal y la membrana postsináptica debido a la sobrecarga de calcio. La piridostigmina debe evitarse en este síndrome, y la quinidina o la fluoxetina son las terapias recomendadas actualmente. CASO CLÍNICO: Niña de 11 años con un fenotipo de cinturas de síndrome miasténico congénito de canal lento que presenta debilidad y fatiga lentamente progresivas desde los 8 años. Tras un empeoramiento clínico con piridostigmina, iniciado empíricamente antes de que los resultados de la secuenciación del exoma estuvieran disponibles, se observó una respuesta espectacular y sostenida con efedrina en monoterapia. La secuenciación del exoma reveló una mutación heterocigota de novo en el gen CHRNB1: c.865G>A; p.Val289Met (NM_000747.2). El estudio electromiográfico con estimulación repetitiva en el nervio peroneo mostró una disminución anormal en la amplitud (23,9%) y también la génesis de un segundo potencial de acción muscular compuesto más pequeño después del pico de la onda M principal en los nervios motores mediano, cubital y peroneo. CONCLUSIÓN: Aunque se han documentado respuestas favorables a agonistas adrenérgicos en asociación con la fluoxetina, ésta representa la primera aportación que documenta una respuesta clínica relevante con efedrina en monoterapia en un paciente con síndrome miasténico congénito de canal lento. Los agonistas adrenérgicos pueden considerarse una opción terapéutica en pacientes con este síndrome

INTRODUCTION: Slow-channel congenital myasthenic syndrome is an autosomal dominant inherited progressive neuromuscular disorder caused by abnormal gating of mutant acetylcholine receptors in the neuromuscular junction. Its pathological hallmark is selective degeneration of the endplate and postsynaptic membrane due to calcium overload. Pyridostigmine should be avoided in this syndrome, being quinidine or fluoxetine the current recommended therapies. CASE REPORT: An 11-year-old girl with a limb-girdle phenotype of slow-channel congenital myasthenic syndrome presenting with a slowly progressive fatigable weakness at the age of 8 years. After a clinical worsening with pyridostigmine, empirically started before the exome sequencing results were available, a dramatic and sustained response to ephedrine monotherapy was observed. Whole exome sequencing revealed a de novo heterozygous mutation in CHRNB1 gene: c.865G>A; p.Val289Met (NM_000747.2). An abnormal decrement in amplitude (23.9%) from the first to fifth intravollley waveform was revealed after repetitive peroneal nerve stimulation at low frequencies. In addition, a second smaller compound muscle action potential after the peak of the main M-wave in median, ulnar and peroneal motor nerves was observed. CONCLUSION: Favorable responses to adrenergic agonists added to fluoxetine had been reported. However, to the best of our knowledge this is the first report on effective monotherapy with ephedrine in a slow-channel congenital myasthenic syndrome patient. Adrenergic agonists may be considered as a therapeutic option in patients with this syndrome

Management of spinal-induced hypotension for elective caesarean section: A survey of practices among anesthesiologists from a developing country.

BACKGROUND: In developing countries, more than half of the anesthesia-related maternal deaths are related to spinal hypotension. OBJECTIVE: To explore the practices of management of spinal induced hypotension with respect to fluid and vasopressor administration among anesthesiologists from a developing country. METHODS: After approval from institutional ethics committee, an online questionnaire was sent to anesthesiologists registered with Pakistan Society of Anesthesiologists between July and August 2018 to determine management strategies for prevention and treatment of spinal-induced hypotension. RESULTS: The response rate was 36% (156/433), majority from academic institution (62.8%) with equal representation from attending and trainee anesthesiologist. For prophylaxis 39.1% respondents did not use vasopressors, 32.7% used fluid preloading with crystalloids (54.7%) as fluid of choice followed by combination of co-loading and vasopressor(22.4%). Phenylephrine was the vasopressor of choice for both prophylaxis (33.1%) and treatment (57%). Attending anesthesiologist used a combination of fluid co-loading and vasopressors for prophylaxis as compared to trainee anesthesiologists (37.2% vs. 17.9%; P=0.035) and selected vasopressors according to patient's heart rate (33.3% vs. 19.5%; p=0.05). Prophylactic phenylephrine was used more by respondents from the academic institution (p=0.023). Fluid co-loading was used more by respondents with <30 % compared to those with > 30% of clinical responsibility to obstetric anesthesia (P<0.05). CONCLUSION: Phenylephrine as the vasopressor of choice indicates growing awareness of management strategies among anesthesiologists from developing countries but there is a need to increase its use for prophylaxis. Some variation in practice according to the level of anesthesiologist, practice type and responsibilities to obstetric anesthesia are evident.

Ephedrine and phenylephrine induce opposite changes in cerebral and paraspinal tissue oxygen saturation, measured with near-infrared spectroscopy: a randomized controlled trial.

While the effects of phenylephrine (PE) and ephedrine (E) on cerebral oxygen saturation (rScO2) already has been studied, the effect on paraspinal oxygen saturation (rSpsO2) is still unexplored. This study aims to assess the effect of PE and E on rScO2 and rSpsO2, measured with near-infrared spectroscopy. A randomized 4-treatment cross-over trial was designed in 28 patients under BIS-titrated anaesthesia with sevoflurane. If MAP decreased more than 20% from baseline, incremental doses of PE and/or E were given according to the randomization (group I: E-PE-E, group II: PE-E-PE, group III: E-E-E, group IV: PE-PE-PE). rScO2 and rSpsO2 on T3-T4, T9-T10 and L1-L2 were recorded. Differences in rSO2 (post-pretreatment) within each group were analyzed with paired Student's t test. Differences in effects of PE and E on rScO2 and rSpsO2 were analyzed with linear mixed-modelling. Following PE administration, rScO2 decreased significantly (- 2.7% ± 3.5), while it remained stable following E (- 0.6% ± 3.6). Contrastingly, rSpsO2 at T3-T4, T9-T10 and L1-L2 slightly increased following PE (0.4% ± 2.5, 0.7% ± 2.0 and - 0.1% ± 1.4, respectively), while it decreased after E administration (- 1.3% ± 3.4%, - 0.7% ± 2.6% and - 1.3% ± 2.7%, respectively). Compared to E, PE administration was associated with a significant decrease in rScO2 (- 2.1%, 95% CI [- 3.1%, - 1.2%], p < 0.001). In contrast, compared to PE, E was associated with a significant decrease in rSpsO2 at T3-T4, T9-T10 and L1-L2 (- 2.0%, 95% CI [- 2.8, - 1.1], p < 0.001; - 1.4%, 95% CI [- 2.4%, - 0.4%], p = 0.006; and - 1.5%, 95% CI [- 2.3%, - 0.8%], p < 0.001, respectively). An opposite effect on rScO2 and rSpsO2 was observed after bolus administration of PE and E.

Nuclear Imaging of the Cardiac Sympathetic Nervous System: A Disease-Specific Interpretation in Heart Failure.

Abnormalities in the cardiac sympathetic nervous system have been documented in various heart diseases and have been directly implicated in their pathogenesis and disease progression. Noninvasive techniques using single-photon-emitting radiotracers for planar scintigraphy and single-photon emission computed tomography, and positron-emitting tracers for positron emissions tomography, have been used to characterize the cardiac sympathetic nervous system with norepinephrine analogs [123I]meta-iodobenzylguanidine for planar and single-photon emission computed tomography imaging and [11C]meta-hydroxyephedrine for positron emissions tomography. Their usefulness in prognostication and risk stratification for cardiac events has been demonstrated. This review bridges basic and clinical research and focuses on applying an understanding of tracer kinetics and neuronal biology, to aid in the interpretation of nuclear imaging of cardiac sympathetic innervation.

Comparison of Hemodynamic Stability and Pain Control in Lateral and Prone Positions in Patients Undergoing Percutaneous Nephrolithotomy: A Randomized Controlled Trial.

PURPOSE: Percutaneous nephrolithotomy (PCNL) is the preferred surgical treatment in many cases of kidney stones which is performed in different positions such as prone, lateral, and supine. This study was designed to evaluate whether patient position (lateral versus . prone) has an effect on the need for analgesia and onset of pain after surgery. MATERIALS AND METHODS: Patient with confirmed kidney stones (size ? 2 cm) who were candidates for PCNL were enrolled in this study. The required biochemical analyses were performed preoperatively. All patients  underwent spinal anesthesia by the same anesthesiologists and then were randomly divided into two separate groups as lateral (L) and prone (P) positions. The operations' start and end time, required time for proper access into target calyces, additional need for analgesic or cardiac drugs, duration of analgesia, and onset of pain after PCNL were carefully recorded and then compared between the two groups. RESULTS: In total, 51 patients were evaluated of whom 39 were men and 12 were women. Mean duration of analgesia after PCNL surgery in P group (173 ± 8 min) was significantly longer than in L group (147±12 min) (P = .001). Furthermore, the amount of ephedrine usage in L group (3.6 ± 1.5mg) was significantly lower than in the P group (16.4 ± 12mg), suggesting more hemodynamic variations in the P group during the operation. CONCLUSION: Our randomized control trial study shows that choosing the optimal position in the PCNL technique depends on  patient's condition. If hemodynamic control is of matter to the anesthesiologist, then lateral position is more appropriate. However, if control of pain and longer time of analgesia are important,  prone position may be preferred.

The influence of the infusion of ephedrine and phenylephrine on the hemodynamic stability after subarachnoid anesthesia in senior adults - a controlled randomized trial.

BACKGROUND: We studied the influence of ephedrine or phenylephrine infusion administered immediately after spinal anesthesia (SA) on hemodynamics in elderly orthopedic patients. METHODS: A prospective, randomized, double-blind, placebo-controlled study. After a subarachnoid injection of 15 mg of levobupivacaine, the participants received an infusion of either ephedrine 20 mg (E group), phenylephrine 250 mcg (P group) or saline (C group) within 30 min. We measured blood pressure, cardiac index (CI) and heart rate (HR) from 15 min before to 30 min after SA. RESULTS: Seventy patients were included in the final analysis. At the end of measurements, mean arterial pressure (MAP) decreased significantly after SA in comparison to the baseline value in the C group but was maintained in the P and E group, with no significant differences between the groups. CI decreased after SA in the C group, was maintained in the P group, and increased significantly in the E group with significant differences between the C and E group (p = 0.049) also between the P and E (p = 0.01) group at the end of measurements. HR decreased significantly after SA in the C and P group but was maintained in the E group, with significant differences between the P and E group (p = 0.033) at the end of measurements. CONCLUSIONS: Hemodynamic changes after SA in elderly orthopedic patients can be prevented by an immediate infusion of phenylephrine or ephedrine. In addition to maintaining blood pressure, the ephedrine infusion also maintains HR and increases CI after SA. TRIAL REGISTRATION: ISRCTN registry with registration number ISRCTN44377602, retrospectively registered on 15 June 2017.

Co-induction with a vasopressor "chaser" to mitigate propofol-induced hypotension when intubating critically ill/frail patients-A questionable practice.

Prophylactic administration of a vasopressor to mitigate the hypotensive effect of propofol (and/or other co-induction agents) during sedation/anesthesia immediately prior to tracheal intubation in frail patients in the intensive care unit and emergency and operating rooms appears to be not an uncommon practice. We submit that this practice is unnecessary and potentially harmful. Despite restoring the blood pressure, phenylephrine, for instance, may have an additive or synergistic effect with propofol in reducing the cardiac output and, ultimately, organ perfusion. Airway instrumentation often leads to sympathetic activation and hypertension (thereby increasing myocardial oxygen consumption) which may be exacerbated by an arbitrary prophylactic dose of phenylephrine. Finally, in spite of the well-recognized need to reduce dosages of propofol in frail patients, excessive doses are commonly given, leading to hypotension. We herein discuss each of these points and suggest alternative techniques to promote a stable induction in frail patients.

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.

A Comparative Study of Bolus Norepinephrine, Phenylephrine, and Ephedrine for the Treatment of Maternal Hypotension in Parturients with Preeclampsia During Cesarean Delivery Under Spinal Anesthesia.

BACKGROUND This study aimed to compare the efficacy and safety of bolus norepinephrine, phenylephrine, and ephedrine in parturient with preeclampsia who had hypotension during cesarean delivery under spinal anesthesia. MATERIAL AND METHODS One hundred and sixty-six parturient women with preeclampsia who had a baseline systolic blood pressure (SBP) <80% during spinal anesthesia for cesarean section were divided into three treatment groups; bolus norepinephrine 4 µg (group N) (n=56), phenylephrine 50 µg (group P) (n=55), and ephedrine 4 mg (group E) (n=55). Primary outcomes included overall SBP and heart rate (HR) until delivery. Secondary outcomes included the incidence of tachycardia (HR >120 bpm), bradycardia (HR <60 bpm), hypertension (SBP >120% baseline), number of boluses of vasopressor required and episodes of hypotension, maternal side effects, and neonatal outcome. RESULTS Overall HR in group N was significantly increased compared with group P (80.5±12 vs. 76.6±6.9 bpm; P=0.04), and significantly lower compared with group E (80.5±12 vs. 84.9±7.1 bpm; P=0.02). Parturients in group N had fewer episodes of bradycardia compared with group P (3.6% vs. 21.8%; RR=0.26l; 95% CI, 0.07-0.73; P=0.004) and fewer episodes of tachycardia compared with group E (16.1% vs. 36.4%; RR 0.54; 95% CI, 0.29-0.90; P=0.02). CONCLUSIONS A bolus dose of norepinephrine showed similar efficacy to phenylephrine but improved maternal and neonatal safety in parturients with preeclampsia with hypotension during cesarean section under spinal anesthesia.

A systematic review of phenytoin intoxication induced by compound phenytoin sodium, ephedrine hydrochloride and theophylline tablets in China.

OBJECTIVE: In this study, we aimed to review the literature on phenytoin intoxication induced by compound phenytoin sodium, ephedrine hydrochloride and theophylline tablets (CPEHTT). METHOD: A literature search was performed in the following databases: WANFANG DATA, HowNet, National Library Reference and Consultation Alliance, Full-text Database of Foreign Medical Journals, PubMed and Ovid. The search terms were "Compound Phenytoin Sodium, ephedrine Hydrochloride and Theophylline Tablets," and "poisoning," or "toxicity," in Chinese and in English. RESULT: Ten articles including 104 patients with CPEHTT intoxication were identified. The ages of the patients ranged from 52 to 82 years. Sixty-seven patients were male and thirty-seven patients were female (the male/female ratio, approximately 2:1). The most common clinical manifestations were dizziness (85%) and ataxia (85%), followed by limb weakness (65%), diplopia (25%), binocular horizontal nystagmus (24%), limb numbness (13%), nausea and vomiting (12%), somnolence (10%), tremor and high muscle tension (7%), lag in response (5%), dysarthria (6%), choking cough (2%), auditory hallucination and visual fantasy (1%), and involuntary movement (1%). All patients had chronic lung disease, and the most common disease was chronic bronchitis. The dosage ranged 4 to 15 tablets per day with medication duration of more than 1 year for most patients. CONCLUSION: The CPEHTT intoxication caused by phenytoin toxicity represents a drug safety problem in China. The common clinical manifestations, serum phenytoin concentrations, and associated factors of CPEHTT intoxication are important for diagnosis and prevention. These findings may help guide clinicians to correctly attend to the use of CPEHTT and avoid its toxicity.

Sinus arrest with prolonged asystole due to the trigeminocardiac reflex during application of local anaesthetic in the nasal mucosa.

The trigeminocardiac reflex (TCR) is defined as a sudden onset of parasympathetic dysrhythmias during stimulation of the trigeminal nerve. We describe a peripheral variation of TCR during manipulation of the nasal mucosa. A 42-year-old patient suffering from severe obstructive sleep apnoea was scheduled for surgical treatment. After inducted anaesthesia, the surgeon infiltrated the nasal mucosa with a local anaesthetic. The patient immediately showed an asystole and was treated with ephedrine and five chest compressions, despite spontaneous sinus rhythm return after ceasing of manipulation. Treatment with atropine established this TCR episode and ensured an event-free surgery.The authors present here, for the first time, a prolonged asystole caused by the TCR, triggered by minimal manipulation of the nasal mucosa. This severe manifestation of peripheral TCR demonstrates its importance in daily clinical business. This case was treated according to a modified treatment algorithm for all subtypes of TCR which is presented here.

The Impact of Ageing on 11C-Hydroxyephedrine Uptake in the Rat Heart.

We aimed to explore the impact of ageing on 11C-hydroxyephedrine (11C-HED) uptake in the healthy rat heart in a longitudinal setting. To investigate a potential cold mass effect, the influence of specific activity on cardiac 11C-HED uptake was evaluated: 11C-HED was synthesized by N-methylation of (-)-metaraminol as the free base (radiochemical purity >95%) and a wide range of specific activities (0.2-141.9 GBq/µmol) were prepared. 11C-HED (48.7 ± 9.7MBq, ranged 0.2-60.4 µg/kg cold mass) was injected in healthy Wistar Rats. Dynamic 23-frame PET images were obtained over 30 min. Time activity curves were generated for the blood input function and myocardial tissue. Cardiac 11C-HED retention index (%/min) was calculated as myocardial tissue activity at 20-30 min divided by the integral of the blood activity curves. Additionally, the impact of ageing on myocardial 11C-HED uptake was investigated longitudinally by PET studies at different ages of healthy Wistar Rats. A dose-dependent reduction of cardiac 11C-HED uptake was observed: The estimated retention index as a marker of norepinephrine function decreased at a lower specific activity (higher amount of cold mass). This observed high affinity of 11C-HED to the neural norepinephrine transporter triggered a subsequent study: In a longitudinal setting, the 11C-HED retention index decreased with increasing age. An age-related decline of cardiac sympathetic innervation could be demonstrated. The herein observed cold mass effect might increase in succeeding scans and therefore, 11C-HED microPET studies should be planned with extreme caution if one single radiosynthesis is scheduled for multiple animals.