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Minerva Anestesiologica Dec 2022Multiple studies have compared varying prophylactic and therapeutic doses of norepinephrine and phenylephrine given as either intermittent bolus or fixed-rate infusion... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Multiple studies have compared varying prophylactic and therapeutic doses of norepinephrine and phenylephrine given as either intermittent bolus or fixed-rate infusion to combat postspinal hypotension in patients undergoing cesarean section (CS). We conducted a systematic review to figure out the best alternative to treat postspinal hypotension.
EVIDENCE ACQUISITION
PubMed and Cochrane databases were extensively searched for eligible RCTs. A total of 15 studies were found eligible and analyzed for the incidence of maternal bradycardia as the primary outcome and other maternal adverse effects, fetal acidosis and Apgar scores at 1 and 5 min as the secondary outcome. Data was analyzed using Review Manager Version 5.3. software.
EVIDENCE SYNTHESIS
There was no significant difference in the efficacy of norepinephrine and phenylephrine for managing postspinal hypotension (OR=1.15 [95% CI: 0.91-1.45], P=0.24, I=0%,moderate quality) in parturients undergoing CS. Odds of incidence of maternal bradycardia decrease significantly by 61% with norepinephrine versus phenylephrine (OR=0.39 [95% CI: 0.31-0.49], P<0.00001, I=27%, high quality evidence). Significant higher umbilical artery mean pH values were observed with NE versus PE (MD=0.0 [95% CI: 0.00 to 0.01], P=0.03), although not clinical relevant. However, no significant difference was found in the incidence of other maternal adverse effects and fetal outcomes.
CONCLUSIONS
Comparable efficacy for management of postspinal hypotension, though, norepinephrine was found to cause less incidence of maternal bradycardia as compared to phenylephrine.
Topics: Humans; Pregnancy; Female; Phenylephrine; Cesarean Section; Norepinephrine; Anesthesia, Spinal; Bradycardia; Vasoconstrictor Agents; Hypotension; Anesthesia, Obstetrical; Double-Blind Method
PubMed: 35785931
DOI: 10.23736/S0375-9393.22.16654-X -
Transplantation Apr 2024We conducted a systematic review and network meta-analyses evaluating the effects of different intraoperative vasoactive drugs on acute kidney injury (AKI) and other... (Meta-Analysis)
Meta-Analysis
We conducted a systematic review and network meta-analyses evaluating the effects of different intraoperative vasoactive drugs on acute kidney injury (AKI) and other perioperative outcomes in adult liver transplant recipients. We searched multiple electronic databases using words from the "liver transplantation" and "vasoactive drug" domains. We included all randomized controlled trials conducted in adult liver transplant recipients comparing 2 different intravenous vasoactive drugs or 1 against a standard of care that reported AKI, intraoperative blood loss, or any other postoperative outcome. We conducted 4 frequentist network meta-analyses using random effect models, based on the interventions' mechanism of action, and evaluated the quality of evidence (QoE) using Grading of Recommendations, Assessment, Development, and Evaluations recommendations. We included 9 randomized controlled trials comparing different vasopressor drugs (vasoconstrictor or inotrope), 3 comparing a somatostatin infusion (or its analogues) to a standard of care, 11 comparing different vasodilator infusions together or against a standard of care, and 2 comparing vasoconstrictor boluses at graft reperfusion. Intravenous clonidine was associated with shorter duration of mechanical ventilation, intensive care unit, and hospital length of stay (very low QoE), and some vasodilators were associated with lower creatinine level 24 h after surgery (low to very low QoE). Phenylephrine and terlipressin were associated with less intraoperative blood loss when compared with norepinephrine (low and moderate QoE). None of the vasoactive drugs improve any other postoperative outcomes, including AKI. There is still important equipoise regarding the best vasoactive drug to use in liver transplantation for most outcomes. Further studies are required to better inform clinical practice.
Topics: Adult; Humans; Liver Transplantation; Blood Loss, Surgical; Network Meta-Analysis; Vasoconstrictor Agents; Vasodilator Agents; Acute Kidney Injury
PubMed: 37525360
DOI: 10.1097/TP.0000000000004744 -
JBI Evidence Synthesis Jan 2021The objective of this review was to examine the effect of phenylephrine on cerebral oxygen saturation, cardiac output, and middle cerebral artery blood flow velocity...
OBJECTIVE
The objective of this review was to examine the effect of phenylephrine on cerebral oxygen saturation, cardiac output, and middle cerebral artery blood flow velocity when used to treat intraoperative hypotension.
INTRODUCTION
While the etiology of postoperative cognitive dysfunction in adults following surgery is likely multifactorial, intraoperative cerebral hypoperfusion is a commonly proposed mechanism. Research evidence and expert opinion are emerging that suggest phenylephrine adversely affects cerebral oxygen saturation and may also adversely affect cerebral perfusion via a reduction in cardiac output or cerebral vascular vasoconstriction. The administration of phenylephrine to treat intraoperative hypotension is common anesthesia practice, despite a lack of evidence to show it improves cerebral perfusion. Therefore, a systematic review of the effect of phenylephrine on cerebral hemodynamics has significant implications for anesthesia practice and future research.
INCLUSION CRITERIA
Studies of adults 18 years and over undergoing elective, non-neurosurgical procedures involving anesthesia were included. In these studies, participants received phenylephrine to treat intraoperative hypotension. The effect of phenylephrine on cerebral oxygen saturation, cardiac output, or middle cerebral artery blood flow velocity was measured.
METHODS
Key information sources searched included MEDLINE (Ovid), Embase, CINAHL (EBSCO), and Google Scholar. The scope of the search was limited to English-language studies published from 1999 through 2017. The recommended JBI approach to critical appraisal, study selection, data extraction, and data synthesis were used.
RESULTS
This systematic review found that phenylephrine consistently decreased cerebral oxygen saturation values despite simultaneously increasing mean arterial pressure to normal range. Results also found that ephedrine and dopamine were superior to phenylephrine in maintaining or increasing values. Phenylephrine was found to be similar to vasopressin in the extent to which both decreased cerebral oxygen saturation values. Results also showed that phenylephrine resulted in statistically significant declines in cardiac output, or failed to improve abnormally low preintervention values. The effect of phenylephrine on middle cerebral artery blood flow velocity was only measured in one study and showed that phenylephrine increased flow velocity by about 20%. Statistical pooling of the study results was not possible due to the gross variation in how the intervention was administered and how effect was measured.
CONCLUSIONS
This review found that phenylephrine administration resulted in declines in cerebral oxygen saturation and cardiac output. However, the research studies were ineffective in informing phenylephrine's mechanism of action or its impact on postoperative cognitive function.
SYSTEMATIC REVIEW REGISTRATION NUMBER
PROSPERO (CRD42018100740).
Topics: Adolescent; Adult; Cardiac Output; Humans; Hypotension; Oxygen; Phenylephrine; Vasoconstrictor Agents
PubMed: 32941358
DOI: 10.11124/JBISRIR-D-19-00352 -
European Stroke Journal Jun 2022Low blood pressure (BP) in acute ischaemic stroke (AIS) is associated with poor functional outcome, death, or severe disability. Increasing BP might benefit patients... (Review)
Review
BACKGROUND
Low blood pressure (BP) in acute ischaemic stroke (AIS) is associated with poor functional outcome, death, or severe disability. Increasing BP might benefit patients with post-stroke hypotension including those with potentially salvageable ischaemic penumbra. This updated systematic review considers the present evidence regarding the use of vasopressors in AIS.
METHODS
We searched the Cochrane Database of Systematic Reviews, MEDLINE, EMBASE and trial databases using a structured search strategy. We examined reference lists of relevant publications for additional studies examining BP elevation in AIS.
RESULTS
We included 27 studies involving 1886 patients. Nine studies assessed increasing BP during acute reperfusion therapy (intravenous thrombolysis, mechanical thrombectomy, intra-arterial thrombolysis or combined). Eighteen studies tested BP elevation alone. Phenylephrine was the most commonly used agent to increase BP (n = 16 studies), followed by norepinephrine (n = 6), epinephrine (n = 3) and dopamine (n = 2). Because of small patient numbers and study heterogeneity, a meta-analysis was not possible. Overall, BP elevation was feasible in patients with fluctuating or worsening neurological symptoms, large vessel occlusion with labile BP, sustained post-stroke hypotension and ineligible for intravenous thrombolysis or after acute reperfusion therapy. The effects on functional outcomes were largely unknown and close monitoring is advised if such intervention is undertaken.
CONCLUSION
Although theoretical arguments support increasing BP to improve cerebral blood flow and sustain the ischaemic penumbra in selected AIS patients, the data are limited and results largely inconclusive. Large, randomised controlled trials are needed to identify the optimal BP target, agent, duration of treatment and effects on clinical outcomes.
PubMed: 35647316
DOI: 10.1177/23969873221078136 -
Frontiers in Pharmacology 2022Phenylephrine is the first-line drug used to maintain blood pressure in cesarean delivery. However, it poses a high risk of bradycardia and depression of cardiac...
Comparative efficacy and safety of prophylactic norepinephrine and phenylephrine in spinal anesthesia for cesarean section: A systematic review and meta-analysis with trial sequential analysis.
Phenylephrine is the first-line drug used to maintain blood pressure in cesarean delivery. However, it poses a high risk of bradycardia and depression of cardiac activity in pregnant women. Consequently, norepinephrine has gained popularity over the recent years, as an alternative to Phenylephrine because it is thought that prophylactic use of vasopressors may reduce the incidence of hypotension after spinal anesthesia. This systematic review compared the efficacy of both treatments. We searched the following databases; CNKI, PubMed, Embase, Web of science, clinicaltrials.gov, Medline and Cochrane Library, for randomized controlled trials comparing the prophylactic efficacy of norepinephrine and phenylephrine on elective cesarean delivery under spinal anesthesia. The search period was from inception to July 2022, and the primary outcome indicator was incidence of bradycardia. Statistical analysis was conducted on Rev manager 5.4, and the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework was used to evaluate the quality of evidence from each main finding. A total of 12 papers were included in the analysis. The incidence of bradycardia (RR = 0.37, 95% CI: 0.28 to 0.49, < 0.00001) and reactive hypertension (RR = 0.58, 95% CI 0.40 to 0.83, = 0.003) was significantly lower in the norepinephrine (NE) group compared with the phenylephrine (PE) category. In contrast, there were no statistical differences in the umbilical cord blood gas analysis pH values between the groups (arterial: MD = 0.00, 95% CI -0.00 to 0.01, = 0.22, vein: MD = 0.01, 95% CI -0.00 to 0.02, = 0.06). The incidence of hypotension, nausea, and vomiting did not differ significantly between the NE and PE groups (hypotension: 23% vs. 18%; nausea: 14% vs. 18%; vomiting: 5% vs. 7%, respectively). Prophylactic use of norepinephrine is safe and effective in maintaining maternal hemodynamics without causing adverse events to either the pregnant woman or fetus. website https://www.crd.york.ac.uk/prospero/, identifier CRD42022347095.
PubMed: 36518675
DOI: 10.3389/fphar.2022.1015325 -
Neurotrauma Reports 2020Intravenous phenylephrine (PE) is utilized commonly in critical care for cardiovascular support. Its impact on the cerebrovasculature is unclear and its use may have... (Review)
Review
Intravenous phenylephrine (PE) is utilized commonly in critical care for cardiovascular support. Its impact on the cerebrovasculature is unclear and its use may have important implications during states of critical neurological illness. The aim of this study was to perform a scoping review of the literature on the cerebrovascular/cerebral blood flow (CBF) effects of PE in traumatic brain injury (TBI), evaluating both animal models and human studies. We searched MEDLINE, BIOSIS, EMBASE, Global Health, SCOPUS, and the Cochrane Library from inception to January 2020. We identified 12 studies with various animal models and 4 studies in humans with varying TBI pathology. There was a trend toward a consistent increase in mean arterial pressure (MAP) by the injection of PE systemically, and by proxy, an increase of the cerebral perfusion pressure (CPP). There was a consistent constriction of cerebral vessels by PE reported in the small number of studies documenting such a response. However, the heterogeneity of the literature on the CBF/cerebral blood volume (CBV) response makes the strength of the conclusions on PE limited. Studies were heterogeneous in design and had significant limitations, with most failing to adjust for confounding factors in cerebrovascular/CBF response. This review highlights the significant knowledge gap on the cerebrovascular/CBF effects of PE administration in TBI, calling for further study on the impact of PE on the cerebrovasculature both and in experimental settings.
PubMed: 34223530
DOI: 10.1089/neur.2020.0008 -
The Cochrane Database of Systematic... Apr 2020Sickle cell disease comprises a group of genetic haemoglobin disorders. The predominant symptom associated with sickle cell disease is pain resulting from the occlusion... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Sickle cell disease comprises a group of genetic haemoglobin disorders. The predominant symptom associated with sickle cell disease is pain resulting from the occlusion of small blood vessels by abnormally 'sickle-shaped' red blood cells. There are other complications, including chronic organ damage and prolonged painful erection of the penis, known as priapism. Severity of sickle cell disease is variable, and treatment is usually symptomatic. Priapism affects up to half of all men with sickle cell disease, however, there is no consistency in treatment. We therefore need to know the best way of treating this complication in order to offer an effective interventional approach to all affected individuals. This is an update of a previously published review.
OBJECTIVES
To assess the benefits and risks of different treatments for stuttering (repeated short episodes) and fulminant (lasting for six hours or more) priapism in sickle cell disease.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register, which comprises references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. We also searched trial registries. Date of the most recent search of the Group's Haemoglobinopathies Trials Register: 09 September 2019. Date of most recent search of trial registries and of Embase: 01 October 2019.
SELECTION CRITERIA
All randomised or quasi-randomised controlled trials comparing non-surgical or surgical treatment with placebo or no treatment, or with another intervention for stuttering or fulminant priapism.
DATA COLLECTION AND ANALYSIS
The authors independently extracted data and assessed the risk of bias of the trials.
MAIN RESULTS
Three trials with 102 participants were identified and met the criteria for inclusion in this review. These trials compared stilboestrol to placebo, sildenafil to placebo and a four-arm trial which compared ephedrine or etilefrine to placebo and ranged in duration from two weeks to six months. All of the trials were conducted in an outpatient setting in Jamaica, Nigeria and the UK. None of the trials measured our first primary outcome, detumescence. However, all three trials reported on the reduction in frequency of stuttering priapism, our second primary outcome; and from the evidence included in this review, we are uncertain whether stilboestrol, etilefrine or ephedrine reduce the frequency of stuttering priapism as the certainty of the evidence has been assessed as very low. Additionally, we conclude that sildenafil may make little or no difference (low-certainty evidence). Two trials reported on immediate side effects and we are uncertain whether etilefrine or ephedrine reduce the occurrence of these (very low-certainty of evidence) and also conclude that sildenafil may make little or no difference in side effects (low-quality evidence). Given that all of the trials were at risk of bias and all had low participant numbers, we considered the certainty of the evidence to be low to very low.
AUTHORS' CONCLUSIONS
There is a lack of evidence for the benefits or risks of the different treatments for both stuttering and fulminant priapism in sickle cell disease. This systematic review has clearly identified the need for well-designed, adequately-powered, multicentre randomised controlled trials assessing the effectiveness of specific interventions for priapism in sickle cell disease.
Topics: Adrenergic Agents; Anemia, Sickle Cell; Diethylstilbestrol; Ephedrine; Estrogens, Non-Steroidal; Etilefrine; Humans; Male; Priapism; Randomized Controlled Trials as Topic; Sildenafil Citrate; Tachycardia; Vasoconstrictor Agents; Young Adult
PubMed: 32251534
DOI: 10.1002/14651858.CD004198.pub4 -
International Journal of Pediatric... Feb 2022Topical intranasal decongestants are essential in nasal surgery to improve operative field. There are concerns regarding safety in paediatric population. Data on safety...
OBJECTIVES
Topical intranasal decongestants are essential in nasal surgery to improve operative field. There are concerns regarding safety in paediatric population. Data on safety and safe dosage are limited. This systematic review evaluated the literature on safety and dosage of intranasal decongestant in paediatric population.
METHODS
We performed a systematic search of PubMed, EMBASE, Cochrane library for relevant articles. Quality assessment was done on included articles.
RESULTS
A total of 10 articles were included: five case reports; three observational studies; and two randomised control trials. Decongestants evaluated were phenylephrine, oxymetazoline, epinephrine, xylometazoline, and cocaine. In total, 209 patients were included. Side effects reported included bradycardia, tachycardia and hypertension. These were mostly self-limiting and of no clinical compromise to the patients. A total of 4/209 (1.9%) of patients required treatment for these reported effects. No mortality was reported in the included studies.
CONCLUSION
In the paediatric population, the literature suggests that when delivered in a pre-specified, controlled dosage, the haemodynamic effects of phenylephrine, oxymetazoline, xylometazoline are minimal and of no clinical significance. There is scope for further studies to establish safe dosage in the paediatric population given the paucity of current literature.
Topics: Administration, Intranasal; Administration, Topical; Child; Humans; Nasal Decongestants; Nasal Surgical Procedures; Oxymetazoline; Vasoconstrictor Agents
PubMed: 34942425
DOI: 10.1016/j.ijporl.2021.111010 -
Anaesthesia Jun 2020Phenylephrine is recommended for the management of hypotension after spinal anaesthesia in women undergoing caesarean section. Noradrenaline, an adrenergic agonist with...
Phenylephrine is recommended for the management of hypotension after spinal anaesthesia in women undergoing caesarean section. Noradrenaline, an adrenergic agonist with weak β-adrenergic activity, has been reported to have a more favourable haemodynamic profile than phenylephrine. However, there are concerns that noradrenaline may be associated with a higher risk of fetal acidosis, defined as an umbilical artery pH < 7.20. We performed a systematic review of trials comparing noradrenaline with phenylephrine, concentrating on primary outcomes of fetal acidosis and maternal hypotension. We identified 13 randomised controlled trials including 2002 patients. Heterogeneity among the studies was high, and there were too few data to calculate a pooled effect estimate. Fetal acidosis was assessed in four studies that had a low risk of bias and a low risk of confounding, that is, studies which used a prophylactic vasopressor and where women received the allocated vasopressor only. There were no significant differences between these studies. No significant differences were observed for hypotension. Two trials found a significantly lower incidence of bradycardia when using noradrenaline. Cardiac output was significantly higher after noradrenaline in two of three studies. For other secondary outcomes including nausea, vomiting and Apgar scores at 1 and 5 min, no studies found significant differences. The evidence so far is too limited to support an advantage of noradrenaline over phenylephrine. Concerns of a deleterious effect of noradrenaline on fetal blood gas status cannot currently be assuaged by the available data from randomised controlled studies.
Topics: Adult; Anesthesia, Obstetrical; Anesthesia, Spinal; Cesarean Section; Female; Humans; Hypotension; Norepinephrine; Phenylephrine; Pregnancy; Vasoconstrictor Agents
PubMed: 32012226
DOI: 10.1111/anae.14976 -
Journal of Clinical Monitoring and... Feb 2024Closed-loop drug delivery systems are autonomous computers able to administer medication in response to changes in physiological parameters (controlled variables). While... (Meta-Analysis)
Meta-Analysis Review
Closed-loop drug delivery systems are autonomous computers able to administer medication in response to changes in physiological parameters (controlled variables). While limited evidence suggested that closed-loop systems can perform better than manual drug administration in certain settings, this technology remains a research tool with an uncertain risk/benefit profile. Our aim was comparing the performance of closed-loop systems with manual intravenous drug administration in adults. We searched MEDLINE, CENTRAL, and Embase from inception until November 2022, without restriction to language. We assessed for inclusion randomised controlled trials comparing closed-loop and manual administration of intravenous drugs in adults, intraoperatively or in the Intensive Care Unit. We identified 32 studies on closed-loop administration of propofol, noradrenaline, phenylephrine, insulin, neuromuscular blockers, and vasodilators. Most studies were at moderate or high risk of bias. The results showed that closed-loop systems reduced the duration of blood pressure outside prespecified targets during noradrenaline (MD 14.9%, 95% CI 9.6-20.2%, I = 66.6%) and vasodilators administration (MD 7.4%, 95% CI 5.2-9.7%, I = 62.3%). Closed-loop systems also decreased the duration of recovery after propofol (MD 1.3 min, 95% CI 0.4-2.1 min, I = 58.6%) and neuromuscular blockers (MD 9.0 min, 95% CI 7.9-10.0 min, I = 0%). The certainty of the evidence was low or very low for most outcomes. Automatic technology may be used to improve the hemodynamic profile during noradrenaline and vasodilators administration and reduce the duration of postanaesthetic recovery.Registration: This systematic review was registered with PROSPERO (CRD42022336950) on the 7th of June 2022.
Topics: Adult; Humans; Propofol; Pharmaceutical Preparations; Neuromuscular Blocking Agents; Norepinephrine; Vasodilator Agents; Randomized Controlled Trials as Topic
PubMed: 37695449
DOI: 10.1007/s10877-023-01069-3