Comparative Hemodynamic Effects Research Articles

Comparing the effects of three local anaesthetic agents on cardiac conduction system - A randomised study.

This study aimed to compare the effects of three local anaesthetic (LA) agents, namely bupivacaine, levobupivacaine, and ropivacaine, on the cardiac conduction system as assessed by corrected QT (QTc) and P wave dispersion (PWD) intervals in lower limb orthopaedic surgeries and to find the most suitable LA agent that can be used for a long duration. The study included 75 patients with American Society of Anesthesiologists physical status I and II of either gender in the age group of 18-65 years undergoing elective lower limb orthopaedic surgeries under epidural anaesthesia. These were allocated to groups B (bupivacaine), L (levobupivacaine), and R (ropivacaine). We observed blood pressure, heart rate, respiratory rate, PWD, and QTc intervals from baseline value through Holter monitoring, pain assessment by visual analogue scale, and demand and total volume of LA consumed by patient-controlled analgesia devices. The repeated measures of ANOVA were carried out to find the effect of time and time-to-group interaction among the groups across the periods. On intergroup comparison of QTc and PWD, no significant difference among groups was observed, but on intragroup analysis, a statistically significant increase in QTc and PWD from baseline was observed for each of groups B, L, and R at all time intervals. However, the mean increase in QTc and PWD recorded for Group B was higher than in groups L and R. Bupivacaine has the maximal tendency to prolong QTc and PWD. All three agents showed comparable haemodynamic effects and time to onset of sensory and motor blockade.

Comparison of ropivacaine with ropivacaine–dexamethasone combination for postoperative analgesia in the pectoral nerve block for modified radical mastectomy: A randomized clinical trial

Abstract Background and Aims: The pectoral nerve block types I and II are novel techniques to provide analgesia for modified radical mastectomy (MRM) surgeries performed under general anesthesia. The primary objective of this study was to compare the duration of effective analgesia, and the secondary objectives were to evaluate the total amount of rescue analgesics in 24 h, hemodynamic changes, and postoperative adverse effects. Methods: This prospective, randomized, double-blind study was conducted on a total of 80 women with breast cancer belonging to American Society of Anesthesiologist class I and II scheduled for MRM, which were randomly allocated into two groups – Group R (n = 40) received 0.25% ropivacaine 29 ml + NS 1 ml and Group RD (n = 40) received 0.25% ropivacaine 29 ml + dexamethasone (4 mg) 1 ml. Ten milliliters of the study drug was used in Pecs I and the rest 20 ml in Pecs II block posttumor resection. Results: The duration of analgesia was statistically significantly longer in RD (778.75 ± 55.12 min) compared to Group R (412.63 ± 21.69 min) (P < 0.05). Pain scores were significantly less in Group RD. The mean dose of acetaminophen required was significantly less in Group RD (2362.50 ± 375.32 mg) than in Group R (3525.00 ± 298.50 mg) (P < 0.05). The incidence of adverse events was similar in both groups. Conclusion: The addition of dexamethasone with ropivacaine in the Pecs block can be used for prolonging the effective duration of analgesia and decreasing postoperative analgesic consumption with comparable hemodynamic and side effect profiles.

Comparative hemodynamic effects of carbetocin vs oxytocin in mothers with stenotic valvular heart disease undergoing cesarean delivery: a randomized controlled trial

Background & objective: Postpartum hemorrhage (PPH) is quite common an obstetric emergency, and is a nightmare for the anesthesiologist as well as the obstetrician. We compared the hemodynamic profiles of oxytocin and carbetocin for prevention of postpartum hemorrhage during elective cesarean delivery in patients with mild to moderate mitral or aortic stenosis. Methodology: This randomized controlled trial included full term pregnant women with known mild to moderate mitral or aortic valve stenosis and undergoing elective cesarean delivery. After delivery of the shoulder of the baby, the participant received either oxytocin or carbetocin. Patients’ hemodynamic parameters, including blood pressure, heart rate, cardiac output, and systemic vascular resistance, were recorded. The primary outcome was the 5-min average cardiac output after the drug administration. Secondary outcomes were cardiac output, systolic blood pressure, heart rate and systemic vascular resistance, blood loss, and the need for rescue uterotonics. Results: Forty-five patients (23 patients in the carbetocin group and 22 in the oxytocin group) were analyzed. The 5-min average cardiac output after drug injection was comparable between the two groups. The number of participants needing rescue uterotonic boluses were significantly more in the oxytocin group than in the carbetocin group (P = 0.022). Conclusion: In full-term pregnant women with stenotic valvular pathologies, carbetocin showed superior uterotonic effect compared to oxytocin; however, both drugs resulted in the equivalent hemodynamic effects. Trial registration: Clinical trial registration with clinicaltrials.gov No. NCT05110482 Keywords: oxytocin; carbetocin; mitral stenosis; aortic stenosis; cesarean delivery; hemodynamics Citation: Refaat S, Amin S, Tarek H, El Regal EA, Eissa AA, Zayed M, Ibrahim M. Comparative hemodynamic effects of carbetocin vs oxytocin in mothers with stenotic valvular heart disease undergoing cesarean delivery: a randomized controlled trial. Anaesth. pain intensive care 2024;28(4):681−686; DOI: 10.35975/apic.v28i4.2369 Received: January 03, 2024; Reviewed: May 05, 2024; Accepted: June 11, 2024

Evaluating the efficacy of a standardized 4 mL/kg fluid bolus technique in critically ill patients with elevated PvaCO2: secondary analysis of two prospective studies.

Limiting the fluid bolus (FB) volume may attenuate side effects, including hemodilution and increased filling pressures, but it may also reduce hemodynamic responsiveness. The minimum volume to create hemodynamic effects is considered to be 4 mL/kg. In critically ill patients, the hemodynamic effects of FB with this volume have not been adequately investigated and compared to higher quantities. We hypothesized that a standardized FB approach using 4 mL/kg has comparable hemodynamic and metabolic effects to the common practice of physician-determined FB in critically ill patients. We conducted post hoc analysis of two trials in non-selected critically ill patients with central venous-to-arterial CO2 tension (PvaCO2) >6 mmHg and no acute bleeding. All patients received crystalloids either at a physician-determined volume and rate or at 4 mL/kg pump-administered at 1.2 L/h. Cardiac index (CI) was calculated with transthoracic echocardiogram, and arterial and venous blood gas samples were assessed before and after FB. Endpoints were changes in CI and oxygen delivery (DO2) >15%. A total of 47 patients were eligible for the study, 15 of whom received physician-determined FB and 32 of whom received standardized FB. Patients in the physician-determined FB group received 16 (12-19) mL/kg at a fluid rate of 1.5 (1.5-1.9) L/h, compared to 4.1 (3.7-4.4) mL/kg at a fluid rate of 1.2 (1.2-1.2) L/h (p < 0.01) in the standardized FB group. The difference in CI elevations between the two groups was not statistically significant (8.8% [-0.1-19.9%] vs. 8.4% [0.3-23.2%], p = 0.76). Compared to physician-determined FB, the standardized FB technique had similar probabilities of increasing CI or DO2 by >15% (odds ratios: 1.3 [95% CI: 0.37-5.18], p = 0.66 and 1.83 [95% CI: 0.49-7.85], p = 0.38). A standardized FB protocol (4 mL/kg at 1.2 L/h) effectively reduced the volume of fluid administered to critically ill patients without compromising hemodynamic or metabolic effects.

"Comparative Hemodynamic Effects of Yoga and Zumba in Middle-Aged Women"

"Comparative Hemodynamic Effects of Yoga and Zumba in Middle-Aged Women"

Preemptive Ketamine in Abdominal Hysterectomy Patients, Does the Route of Administration Affect Analgesia and Hemodynamics? A Prospective Randomized Controlled Trial

Introduction: Hysterectomy is a common procedure and postoperative pain is a considerable problem. Preemptive analgesia includes analgesic administration prior to surgical stimulus. Ketamine is a short acting anesthetic drug with analgesic and anti-inflammatory properties, reducing central sensitization of pain pathway and hyperalgesia. Objectives: This study aimed to assess the efficacy of preemptive use of ketamine as an analgesic drug, either by intravenous route or by subcutaneous infiltration at the incisional site, regarding perioperative hemodynamics, postoperative pain and gastrointestinal irritation symptoms. Patients and methods: 60 patients were enrolled in this study, divided into two equal groups (30 each) according to route of preemptive ketamine administration. Group (V) received 0.5 mg.kg-1 intravenously while group (S) received 0.5 mg.kg-1 subcutaneously at incisional site. Postoperative pain assessment for 24 H. using visual analogue score (VAS) was adapted as primary outcome objective, while secondary outcomes included hemodynamic parameter and postoperative nausea and vomiting (PONV). Results: Data were analysed. VAS score showed significant difference among studied groups in early 2 postoperative hours. VAS0 (V 2.40±0.62, S 1.96±0.92, P 0.038), VAS1 (V 3.96±1.21, S 2.86±0.89, P 0.001), VAS2 (V 4.00±0.94, S 3.33±0.88, P 0.007). Also, first time to pethidine intake (V 1.50±0.93 H, S 2.36±1.27 H, P 0.004). Other study objectives were comparable. Conclusion: Preemptive use of ketamine with subcutaneous infiltration at incisional site in total abdominal hysterectomy patients provided better analgesia in early postoperative hours rather than intravenous route with comparable hemodynamic parameter and side effects.

The hemodynamic and analgesic efficacy of subcutaneous dexmedetomidine versus Marcaine 0.5% in postoperative pain management following herniorrhaphy

Background: This study addressed the comparative hemodynamic and analgesic effects of subcutaneous dexmedetomidine versus Marcaine 0.5% on herniorrhaphy scheduled patients, as well as postoperative pain management. Materials and Methods: A double-blind trial was conducted in three groups of patients (n = 120) scheduled for herniorrhaphy. The study groups were (i) Marcaine + dexmedetomidine (MAR-DEX) group, receiving Marcaine 0.5% (5 mg) + dexmedetomidine (1 mcg/kg), (ii) MAR group, Marcaine 0.5% (5 mg), and (iii) PBO group, placebo, subcutaneously. Vital signs (blood pressure/heart rate/SaO2), as well as pain scores (using the Visual Analog Scale) at recovery and certain time points (1, 2, 4, 6, 12, and 24 h postoperatively) were measured. Moreover, the overall opioid administered postoperatively and the side effects were recorded. Data were analyzed by SPSS (version 20) software by analysis of variance and repeated measurement tests. Results: Lower pain score was revealed in the MAR-DEX group and higher one in the PBO group (P Conclusion: Adding dexmedetomidine had benefits of relieving pain and reducing opioid use without any side effects.

Comparison of intravenous fentanyl versus lidocaine for attenuation of hemodynamic response to laryngoscopy and endotracheal intubation in patients undergoing elective surgery in Dilla University Referral Hospital, Ethiopia, a randomized controlled trial

Background: Laryngoscopy and endotracheal intubation is one of the most stressing moments in technique of general anesthesia. It can cause pressure response and sympato adrenal response due to stimulation of epipharynx and laryngopharynx. The main objective of this study is to compare the effect of intravenous lidocaine and fentanyl for attenuation of hemodynamic response during laryngoscopy and intubation in elective patients who undergo general anesthesia with endotracheal intubation. Methods: A randomized controlled trial was conducted in 52 eligible adults allocated in to 2 group; group F (n=26) patients received fentanyl 2 mcg/kg and group L (n=26) patients received lidocaine (2%) 1.5 mg/kg. The hemodynamic variables were recorded at 1st, 3rd, 5th, and 10th minutes after laryngoscopy and intubation. Kolmogorov test were used to test for distributions of data while homogeneity of variance were assessed using Levene test for equality of variance. Between groups comparison of vital sign were made using independent t test symmetric data and Mann-Whitney U test was used for asymmetric data. A post hoc effect size calculated using G-power. Those variables with P-value &lt;0.05 were considered as statistically significant. Result: The mean rise in heart rate from base line was higher in lidocaine group 29.26±15.02 bpm compared with fentanyl group 17.56±10.28 bpm at first minute. The mean rise in systolic blood pressure from base line at first minute is lower in fentanyl group 17.53±13.04 compared with lidocaine group 31.53±17.24. The mean rise in hemodynamic variables (heart rate, systolic blood pressure, means arterial pressure, and diastolic blood pressure) from base line at 3rd, 5th, and 10th were comparable between groups with (P-value &gt;0.05). Conclusion and Recommendation: Fentanyl at 2 µg/kg is superior in attenuation of hemodynamic response to laryngoscopy and intubation at first minute. There is comparable hemodynamic attenuation effect between groups at 3rd, 5th, and 10th minutes after intubation. Based on this we recommended that use of fentanyl 2 µg/kg better blunt hemodynamic response at first minute where both are equal at 3rd, 5th, and 10th minutes.

Modified electroconvulsive therapy in a resource-challenged setting: Comparison of two doses (0.5 mg/kg and 1 mg/kg) of suxamethonium chloride.

Background:Suxamethonium has been shown to have a superior modification of the convulsion associated with ECT compared to other muscle relaxants. The dosage of suxamethonium used in ECT varies widely based on the experiences of practitioners. The study aimed to determine and compare the effectiveness and side effect profile of 0.5 mg/kg and 1 mg/kg in modified ECT.Subjects and Methods:This was a prospective randomized crossover study, comparing the effects of suxamethonium at a dose of 0.5 mg/kg, and 1.0 mg/kg in 27 patients who had a total of 54 sessions of modified ECT. The primary outcome parameters were quality of convulsion and onset and duration of apnoea. The secondary outcome parameters were hemodynamic variables, arterial oxygen saturation, delayed recovery, muscle pain, vomiting, headache, prolonged convulsion, and serum potassium. Data collected were entered into proforma and analyzed using Statistical Package for Social Sciences (SPSS) version 17.0. Parametric variables are presented as means and standard deviations while non-parametric variables are presented as frequencies and percentages. The level of significance (P-value) was considered at 0.05.Results:Sixteen patients (59%) had acceptable convulsion modification with 0.5 mg/kg suxamethonium compared to 23 patients (85%) with the use of 1.0 mg/kg suxamethonium (P = 0.016). There was no statistically significant difference in the duration of convulsion, the onset of apnoea, and the duration of apnoea with the two doses. Changes in heart rate, blood pressure, arterial oxygen saturation, and serum potassium level that accompany the mECT were comparable with the two doses of suxamethonium studied.Conclusions:A better modification of convulsion with comparable hemodynamic and side effect profile is achieved during mECT with the use of 1.0 mg/kg suxamethonium compared to 0.5 mg/kg.

Direct comparison of the acute subjective, emotional, autonomic, and endocrine effects of MDMA, methylphenidate, and modafinil in healthy subjects

Rationale3,4-Methylenedioxymethamphetamine (MDMA) is used recreationally and investigated as an adjunct to psychotherapy. Methylphenidate and modafinil are psychostimulants that are used to treat attention-deficit/hyperactivity disorder and narcolepsy, respectively, but they are also misused as cognitive enhancers. Little is known about differences in the acute effects of equally cardiostimulant doses of these stimulant-type substances compared directly within the same subjects.MethodsWe investigated the acute autonomic, subjective, endocrine, and emotional effects of single doses of MDMA (125 mg), methylphenidate (60 mg), modafinil (600 mg), and placebo in a double-blind, cross-over study in 24 healthy participants. Acute drug effects were tested using psychometric scales, the Facial Emotion Recognition Task (FERT), and the Sexual Arousal and Desire Inventory (SADI).ResultsAll active drugs produced comparable hemodynamic and adverse effects. MDMA produced greater increases in pupil dilation, subjective good drug effects, drug liking, happiness, trust, well-being, and alterations in consciousness than methylphenidate or modafinil. Only MDMA reduced subjective anxiety and impaired fear recognition and led to misclassifications of emotions as happy on the FERT. On the SADI, only MDMA produced sexual arousal-like effects. Only MDMA produced marked increases in cortisol, prolactin, and oxytocin. In contrast to MDMA, methylphenidate increased subjective anxiety, and methylphenidate and modafinil increased misclassifications of emotions as angry on the FERT. Modafinil had no significant subjective drug effects but significant sympathomimetic and adverse effects.ConclusionsMDMA induced subjective, emotional, sexual, and endocrine effects that were clearly distinct from those of methylphenidate and modafinil at the doses used.

A comparative study of dexmedetomidine and fentanyl as adjuvants to levobupivacaine for caudal analgesia in children undergoing lower limb orthopedic surgery.

Background:Levobupivacaine is an effective local anesthetic agent with less systemic toxicity than racemic bupivacaine, but it has short postoperative analgesic duration. Dexmedetomidine and fentanyl are promising adjuncts to provide excellent and prolonged postoperative caudal analgesia. This study compared the effects of caudal levobupivacaine plus dexmedetomidine and levobupivacaine plus fentanyl for postoperative analgesia and sedation in children undergoing lower limb orthopedic surgery.Patients and Methods:Ninety children, whose age ranged from 1 to 7 years, American Society of Anesthesiologists I-II, undergoing orthopedic lower limb surgery under general anesthesia received caudal block for postoperative analgesia. The children were randomly allocated into three groups: Group L (control) received 0.75 ml/kg levobupivacaine 0.25% diluted in saline; Group LD received 0.75 ml/kg levobupivacaine 0.25% with dexmedetomidine 1 μg/kg; and Group LF received 0.75 ml/kg levobupivacaine 0.25% with fentanyl 1 μg/kg. Following the administration of the drugs; hemodynamic variables, the total anesthesia time, sedation score, Face, Legs, Activity, Cry, Consolability score, duration of analgesia, and side effects were recorded.Results:Demographically, all the groups were comparable, both the baseline and the intraoperative hemodynamic profile were similar in all groups. The mean duration of analgesia and the mean sedation score in the Group LD were significantly greater as compared to both the other groups.Conclusion:Dexmedetomidine may be a better additive to levobupivacaine than fentanyl for caudal postoperative analgesia, arousable sedation with comparable hemodynamic and side effect profile in children.

AT1 receptor antagonism to reduce aortic expansion in Marfan syndrome: lost in translation or in need of different interpretation?

Marfan syndrome is an inherited autosomal dominant disorder of the connective tissue caused by mutations in the gene encoding fibrillin-1 ( FBN1 ).1,2 This disease has affected the ATVB community with the loss of 1 of our highly respected members, David Williams.3 The most devastating health issues of patients with Marfan syndrome are dissection and rupture of the proximal aorta. Aortic dimensions are routinely monitored in patients with Marfan syndrome, and surgical graft imposition is performed to sustain life. However, surgical intervention is a formidable process. To abrogate surgical repair, there is a desperate need for a medical approach for attenuating aortic expansion. Presently, patients with Marfan syndrome are routinely provided with β-adrenoceptor blockade. This standard of care is derived from the study of Shores et al.4 However, the benefit derived from administration of β-adrenoceptor blockade is far from established. Although FBN1 is a component of extracellular matrix, mutations in this protein do not directly promote the structural fragility that characterizes the specific aortic regions of patients with Marfan syndrome. Instead, a concept has developed that Fbn1 mutations lead to enhanced transforming growth factor β (TGF-β) activation that is the mechanistic basis of Marfan pathology. This concept originated from the demonstration that Fbn1 deficiency led to excessive activation of TGF-β signaling because of reduced binding, sequestration, and inactivation of TGF-β.5 Activation of TGF-β in Fbn1 -deficient mice was associated with a lung pathology similar to that observed in some patients with Marfan syndrome. This paradigm of FBN1 regulation of TGF-β activation was extended to aortic disease by generating heterozygous mice that express a C1039G mutation.6 These mice develop pronounced dilation of the ascending aorta associated with thickened media containing disrupted elastin fibers. In this model, the major proof of concept for the role of …

Delayed Trans-Septal Activation Results in Comparable Hemodynamic Effect of Left Ventricular and Biventricular Endocardial Pacing

Background— We sought to compare left ventricular (LV epi ) and biventricular epicardial pacing (BIV epi ) with LV (LV endo ) and BIV endocardial pacing (BIV endo ) in patients with chronic heart failure with an emphasis on the underlying electrophysiological mechanisms and hemodynamic effects. Methods and Results— Ten patients with chronically implanted cardiac resynchronization devices underwent temporary LV endo and BIV endo pacing with an LV endocardial roving catheter. A pressure wire and noncontact mapping array were placed to the LV cavity to measure LVdP/dt max and perform electroanatomical mapping. At the optimal endocardial position, the acute hemodynamic response (AHR) was superior to epicardial stimulation, the AHR to BIV endo pacing and LV endo pacing being comparable (21±15% versus 22±17%; P =NS). During intrinsic conduction, QRS duration was 185±30 ms, endocardial LV total activation time 92±27 ms, and trans-septal activation time 60±21 ms. With LV endo pacing, QRS duration (187±29 ms; P =NS) and endocardial LV total activation time (91±23 ms; P =NS) were comparable with intrinsic conduction. There was no significant difference in endocardial LV total activation time between LV endo and BIV endo pacing (91±23 versus 85±15 ms; P =NS). Assessment of isochronal maps identified slow trans-septal conduction with both LV endo and BIV endo pacing resulting in activation of almost the entire LV endocardium prior to septal breakout, thereby limiting any possible fusion with either pacing mode. Conclusions— The equivalent AHR to LV endo and BIV endo pacing may be explained by prolonged trans-septal conduction limiting fusion of electrical wavefronts. The optimal AHR was associated with predominantly LV pre-excitation and depolarization. Our results suggest that LV pacing alone may offer a viable endocardial stimulation strategy to achieve cardiac resynchronization.

Comparative hemodynamic effects of percutaneously delivered circulatory support devices

Comparative hemodynamic effects of percutaneously delivered circulatory support devices

Comparison of the Haemodynamic Effects of Pyrethroid Insecticide and Amodiaquine in Rats

Malaria infection is a common cause of morbidity and mortality especially in the tropics and subtropics. This has led to the increased prophylactic use ofpyrethroid insecticides and/or Amodiaquine (Aq) to combat the parasitic protozoan infection. The aim of this study was to investigate the comparative haemodynamic effects of pyrethroid insecticide and amodiaquine in rats. Experimental rats were randomly allocated into seven groups of five rats in each. Groups 1, 2 and 3 were exposed to pyrethroid by inhalation for 1, 2 and 3 min, respectively, while groups 4, 5 and 6 were administered Aqper oral at 5, 10 and 15 mg kg(-1) b.wt., respectively. Control rats were neither exposed to pyrethroid nor administered Aq. Pyrethroid insecticide led to reduced systolic, diastolic and mean arterial pressures, but increased pulse pressure. Aq treatment did not cause any significant variation in haemodynamic variables. Heart rate was comparable in all groups. Results from the study provide extended safety/toxicity profile for pyrethroid use and Aq treatment. Aq showed no cardiotoxic potential, while pyrethroids have hypotensive effect. It is thus recommended that exposure to pyrethroids should be minimized.

Milrinone is preferred to levosimendan for mesenteric perfusion in hypoxia-reoxygenated newborn piglets treated with dopamine

INTRODUCTIONThere is little information regarding the comparative hemodynamic effects of adding milrinone or levosimendan to dopamine infusion in hypoxia-reoxygenated (H-R) newborns.RESULTSSeverely hypoxic piglets had cardiogenic shock with depressed cardiac index (CI) and mean arterial pressure (MAP). The hemodynamics deteriorated gradually after initial recovery upon reoxygenation. Heart rate and CI improved with milrinone (D+M) and levosimendan (D+L) administration (P < 0.05 vs. control). Both regimens improved carotid arterial flow and carotid vascular resistance; D+M additionally improved superior mesentric arterial flow (all P < 0.05 vs. control). No effect was found on renal arterial flow or elevated lactate state with either regimen. D+M piglets also had a lower myocardial oxidized/reduced glutathione ratio (P < 0.05 vs. control).DISCUSSIONIn conclusion, adding milrinone or levosimendan to dopamine similarly improved systemic hemodynamics in H-R newborn piglets. Milrinone also improved mesenteric perfusion and attenuated myocardial oxidative stress.METHODSTwenty-eight piglets (1–4 d, 1.5–2.5 kg) were instrumented for continuous monitoring of systemic MAP and pulmonary arterial pressure (PAP), CI, and carotid, superior mesenteric, and renal arterial flows. Piglets were randomized with blinding to sham-operated, H-R control (saline), and H-R dopamine (10 μg/kg/min) with D+M or D+L groups. H-R piglets underwent H-R followed by 2 h of drug infusion after reoxygenation. Tissue was collected for biochemical/oxidative stress testing and histological analysis.

Haemodynamic effects of carbetocin and oxytocin given as intravenous bolus on women undergoing caesarean delivery: a randomised trial

This study compares the maternal heart rate effects of carbetocin and oxytocin during elective caesarean delivery. Double blind randomised single centre study (1:1). University hospital providing intrapartum care. Fifty-six women undergoing elective caesarean section after spinal anaesthesia. Haemodynamic parameters were measured non-invasively using the Task Force(®) Monitor 3040i system. Measurements were taken for 500 seconds upon administration of a slow intravenous bolus of the clinically recommended doses of 100 μg of carbetocin or 5 IU of oxytocin to prevent postpartum haemorrhage (PPH). Effect on maternal heart rate (HR). Statistically indistinguishable haemodynamic effects were seen for both drugs, with a maximal effect at about 30-40 seconds: HR increased 17.98 ± 2.53 bpm for oxytocin and 14.20 ± 2.45 bpm for carbetocin. Systolic blood pressure (sBP) decreased (-26.80 ± 2.82 mmHg for oxytocin versus -22.98 ± 2.75 mmHg for carbetocin). Following the maximal effect, women treated with carbetocin recovered slowly to baseline values asymptotically (HR and BP), whereas women treated with oxytocin displayed a slight rebound bradycardia at 200 seconds (-6.8 ± 1.92 bpm). Patients under both treatments showed a similar profile of side effects without any indication of unexpected adverse effects. Both oxytocins have comparable haemodynamic effects and are uterotonic drugs with an acceptable safety profile for prophylactic use. Minimal differences in the recovery phase beyond 70 seconds are in keeping with the fact that carbetocin has an extended half-life compared with oxytocin.

Comparative Hemodynamic Effects of Levosimendan Alone and in Conjunction with 4-Aminopyridine or Calcium Chloride in a Rodent Model of Severe Verapamil Poisoning

Levosimendan (Levo) increases sensitivity of troponin-C to calcium, thus increasing myocardial contractility. It is also a vascular K+-ATP channel agonist producing peripheral vasodilation. Previous research with levosimendan revealed an increase in cardiac output (CO) but not blood pressure (BP) in experimental verapamil poisoning. Levosimendan's K+-channel agonist properties may augment verapamil's vasodilatory effects. 4-Aminopyridine (4-AP) is a K+-channel antagonist. It has successfully reversed hypotension in experimental verapamil poisoning. We hypothesized that coadministration of these agents may improve BP and CO in verapamil poisoning. Anesthetized, ventilated, and canulated male Wistar rats were poisoned with verapamil. Animals received one of six treatments, which are as follows: (1) n-saline infusion (control), (2) Levo 6.25 μg/kg loading dose and 36 μg/kg/h infusion, (3) 4-AP 2 mg/kg loading dose and infusion (4-AP), (4) Levo+4-AP, (5) CaCl₂ loading dose and infusion, and (6) Levo+CaCl(2). Hemodynamic parameters were recorded for 60 min. Outcome measures were changes in CO, BP, and heart rate (HR) compared to control. All groups had similar pretoxicity and peak toxicity CO (50% of pretoxicity value), BP (50% or pretoxicity value), and HR. Control group CO, BP, and HR progressively dropped during the verapamil infusion. Levosimendan produced a statistically significant improvement in CO (75% of pretoxicity level) but not BP in comparison to control. 4-AP produced a significant improvement in CO (110% of pretoxicity) and BP (78% of pretoxicity). Levo+4-AP and Levo+CaCl₂ groups improved CO (100% of pretoxicity) and BP (77% and 50% of pretoxicity, respectively), but there was no additive increase in CO or BP in animals compared to 4-AP or CaCl₂ alone. Levosimendan moderately improved CO but not BP in verapamil poisoning. The hypotensive effects of levosimendan were not overcome by coadministration of either 4-AP or CaCl₂. Levosimendan may not be an appropriate agent to use in the treatment of verapamil poisoning.

Treprostinil for the treatment of pulmonary hypertension

Background: Pulmonary hypertension (PH) is a severely disabling disorder characterized by sustained elevations of pulmonary arterial pressure, ultimately leading to right-heart failure and death. Pulmonary arterial hypertension (PAH) usually occurs in the absence of an evident cause (idiopathic PAH) or may be associated with connective tissue disease, HIV infection, congenital heart disease, chronic liver disease or result from the use of toxic agents and anorexigens. Objective/method: Intravenous epoprostenol has been widely used in patients with PAH, leading to long-term clinical benefits and improved survival. Epoprostenol has to be delivered through a permanently implanted Intravenous catheter. This may expose patients to potentially life-threatening complications. Thus, more stable compounds and alternative modes of prostacyclin delivery have been sought. Conclusion: Treprostinil sodium is a stable prostacyclin analogue, sharing pharmacologic actions similar to epoprostenol with comparable haemodynamic effects. Treprostinil is chemically stable at room temperature and has a long half-life (2 – 4 h), making this drug suitable for subcutaneous administration, with practical benefits in avoiding the risk of line infection and thrombosis, and cardiovascular reactions due to abrupt drug discontinuation.

The Role of Treprostinil in the Management of Pulmonary Hypertension

Pulmonary arterial hypertension (PAH) is a severely disabling disorder characterized by sustained elevations of pulmonary vascular resistance, ultimately leading to right-heart failure and death. Intravenous epoprostenol has been widely used in patients with PAH, leading to long-term clinical benefits and improved survival. Epoprostenol has to be delivered through a permanently implanted intravenous catheter, with the potential of life-threatening complications. Thus, treprostinil, a stable prostacyclin analog suitable for subcutaneous administration, has been developed. Treprostinil is chemically stable at room temperature, has a long half-life (2-4 hours), and has similar pharmacologic properties with comparable hemodynamic effects as epoprostenol.A large, double-blind, placebo-controlled, multicenter, 12-week study confirmed the efficacy of subcutaneous treprostinil, by improving exercise capacity, Borg Dypnea Score (BDS), New York Heart Association (NYHA) class, and clinical signs and symptoms in patients with PAH. Subsequently, multiple observational studies reported the long-term effects of subcutaneous treprostinil. The long-term survival of patients treated with subcutaneous treprostinil was similar to that reported with intravenous epoprostenol. Pain at the infusion site has been a major drawback of subcutaneous treprostinil, hampering dose titration and leading to an 8-10% discontinuation rate. In addition, studies have examined the efficacy of intravenous treprostinil in the treatment of patients with PAH. An open-label study demonstrated that intravenous treprostinil improved exercise capacity, BDS, NYHA functional class, and hemodynamics at week 12 compared with baseline. Transitioning from intravenous epoprostenol to intravenous treprostinil is safe and effective. The dose of intravenous treprostinil has to be adjusted to approximately twice the dose of intravenous epoprostenol. Most patients have reported less severe adverse effects with intravenous treprostinil compared with intravenous epoprostenol. The assessment of the long-term efficacy and safety of continuous intravenous treprostinil requires further studies.