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Cureus Feb 2023Loop diuretics continue to be a crucial component of pharmacological treatment, to eliminate extra fluid and enhance symptom control in acute decompensated heart failure... (Review)
Review
Loop diuretics continue to be a crucial component of pharmacological treatment, to eliminate extra fluid and enhance symptom control in acute decompensated heart failure (ADHF). Understanding the loop diuretics' more efficient form of administration would be very beneficial in improving the management of people's ADHF, resulting in a quicker resolution of symptoms and a notable decrease in morbidity. To assess the outcomes of intravenous continuous infusion with bolus injection of loop diuretics for patients with ADHF, this meta-analysis was carried out. The current meta-analysis was conducted as per the Cochrane Collaboration guidelines and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis extension (PRISMA) guidelines. A search was carried out on PubMed and EMBASE databases for studies comparing continuous infusion with intermittent bolus injection of furosemide in patients with congestive heart failure without restriction on the language of publication from 1 January 2001 to 31 July 2022. The primary outcome of the meta-analysis was all-cause mortality and loss of body weight (kg). Pre-defined secondary outcomes included length of hospital stay (LOS) in days, brain natriuretic peptide (BNP) reduction (pg/ml), number of patients with hypokalemia, and urine output at 24 hours (ml). A total of nine articles were included in this meta-analysis enrolling 713 patients. No significant difference was reported between patients who received intermittent bolus injections and continuous infusion of furosemide in regards to all-cause mortality, LOS, total urine output, the incidence of hypokalemia, and change in BNP. However, the reduction of body weight was greater in the continuous infusion group compared to bolus administration. In conclusion, in the current meta-analysis of nine randomized controlled trials (RCTs), continuous infusion of furosemide seemed to have a greater reduction of body weight. However, no significant difference was there in 24-hrs urine output. However, we cannot conclude that intravenous continuous infusion has a better diuretic effect compared to bolus administration.
PubMed: 36909062
DOI: 10.7759/cureus.34758 -
Journal of Psychopharmacology (Oxford,... Jan 2024N,N-Dimethyltryptamine (DMT) is a serotonergic psychedelic that induces a rapid and transient altered state of consciousness when inhaled or injected via bolus... (Randomized Controlled Trial)
Randomized Controlled Trial
N,N-Dimethyltryptamine (DMT) is a serotonergic psychedelic that induces a rapid and transient altered state of consciousness when inhaled or injected via bolus administration. Its marked and novel subjective effects make DMT a powerful tool for the neuroscientific study of consciousness and preliminary results show its potential role in treating mental health conditions. In a within-subjects, placebo-controlled study, we investigated a novel method of DMT administration involving a bolus injection paired with a constant-rate infusion, with the goal of extending the DMT experience. Pharmacokinetic parameters of DMT estimated from plasma data of a previous study of bolus intravenous DMT were used to derive dose regimens necessary to keep subjects in steady levels of immersion into the DMT experience over an extended period of 30 min, and four dose regimens consisting of a bolus loading dose and a slow-rate infusion were tested in eleven healthy volunteers (seven male, four female, mean age ± SD = 37.09 ± 8.93 years). The present method is effective for extending the DMT experience in a stable and tolerable fashion. While subjective effects were maintained over the period of active infusion, anxiety ratings remained low and heart rate habituated within 15 min, indicating psychological and physiological safety of extended DMT. Plasma DMT concentrations increased consistently starting 10 min into DMT administration, whereas psychological effects plateaued into the desired steady state, suggesting the development of acute psychological tolerance to DMT. Taken together, these findings demonstrate the safety and effectiveness of continuous IV DMT administration, laying the groundwork for the further development of this method of administration for basic and clinical research.
Topics: Female; Humans; Male; Administration, Intravenous; Consciousness; Hallucinogens; Mental Disorders; N,N-Dimethyltryptamine; Adult; Middle Aged
PubMed: 37897244
DOI: 10.1177/02698811231196877 -
Critical Care (London, England) Jul 2023Vasopressin is a second-line vasoactive agent for refractory septic shock. Vasopressin loading is not generally performed because of the lack of evidence for its effects... (Observational Study)
Observational Study
BACKGROUND
Vasopressin is a second-line vasoactive agent for refractory septic shock. Vasopressin loading is not generally performed because of the lack of evidence for its effects and safety. However, based on our previous findings, we hypothesized it can predict the responsibility to vasopressin infusion with safety, and prospectively examined it in the present study.
METHODS
Vasopressin loading was performed via the intravenous administration of a bolus of 1 U, followed by its continuous infusion at 1U/h in patients with septic shock treated with ≥ 0.2 μg/kg/min noradrenaline. An arterial pressure wave analysis was conducted, and endocrinological tests were performed immediately prior to vasopressin loading. We classified patients into responders/non-responders based on mean arterial pressure (MAP) changes after vasopressin loading. Based on our previous findings, the lower tertile of MAP changes was selected as the cut-off. The change in the catecholamine index (CAI) after 6 h was assigned as the primary outcome. Digital ischemia, mesenteric ischemia, and myocardial ischemia during the admission period were prospectively and systematically recorded as adverse events.
RESULTS
Ninety-two patients were registered during the study period and examined. Sixty-two patients with a MAP change > 22 mmHg were assigned as responders and the others as non-responders. Blood adrenocorticotropic hormone levels were significantly higher in non-responders. Stroke volume variations were higher in responders before loading, while stroke volume and dP/dt were higher in responders after loading. Median CAI changes were - 10 in responders and 0 in non-responders, which was significantly lower in the former (p < 0.0001). AUROC of MAP change with vasopressin loading to predict CAI change < 0 after continuous infusion was 0.843 with sensitivity of 0.92 and specificity of 0.77. Ischemia events were observed in 5 cases (5.4%).
CONCLUSIONS
Vasopressin loading may be safely introduced for septic shock. Vasopressin loading may be used to predict responses to its continuous infusion and select appropriate strategies to increase blood pressure.
Topics: Humans; Shock, Septic; Norepinephrine; Vasopressins; Catecholamines; Administration, Intravenous
PubMed: 37480126
DOI: 10.1186/s13054-023-04583-7 -
The Cochrane Database of Systematic... Jan 2023Postoperative pain clinical management in neonates has always been a challenging medical issue. Worldwide, several systemic opioid regimens are available for... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Postoperative pain clinical management in neonates has always been a challenging medical issue. Worldwide, several systemic opioid regimens are available for pediatricians, neonatologists, and general practitioners to control pain in neonates undergoing surgical procedures. However, the most effective and safe regimen is still unknown in the current body of literature.
OBJECTIVES
To determine the effects of different regimens of systemic opioid analgesics in neonates submitted to surgery on all-cause mortality, pain, and significant neurodevelopmental disability. Potentially assessed regimens might include: different doses of the same opioid, different routes of administration of the same opioid, continuous infusion versus bolus administration, or 'as needed' administration versus 'as scheduled' administration.
SEARCH METHODS
Searches were conducted in June 2022 using the following databases: Cochrane Central Register of Controlled Trials [CENTRAL], PubMed, and CINAHL. Trial registration records were identified via CENTRAL and an independent search of the ISRCTN registry.
SELECTION CRITERIA
We included randomized controlled trials (RCTs), quasi-randomized, cluster-randomized, and cross-over controlled trials evaluating systemic opioid regimens' effects on postoperative pain in neonates (pre-term or full-term). We considered suitable for inclusion: I) studies evaluating different doses of the same opioid; 2) studies evaluating different routes of administration of the same opioid; 3) studies evaluating the effectiveness of continuous infusion versus bolus infusion; and 4) studies establishing an assessment of an 'as needed' administration versus 'as scheduled' administration.
DATA COLLECTION AND ANALYSIS
According to Cochrane methods, two investigators independently screened retrieved records, extracted data, and appraised the risk of bias. We stratified meta-analysis by the type of intervention: studies evaluating the use of opioids for postoperative pain in neonates through continuous infusion versus bolus infusion and studies assessing the 'as needed' administration versus 'as scheduled' administration. We used the fixed-effect model with risk ratio (RR) for dichotomous data and mean difference (MD), standardized mean difference (SMD), median, and interquartile range (IQR) for continuous data. Finally, we used the GRADEpro approach for primary outcomes to evaluate the quality of the evidence across included studies.
MAIN RESULTS
In this review, we included seven randomized controlled clinical trials (504 infants) from 1996 to 2020. We identified no studies comparing different doses of the same opioid, or different routes. The administration of continuous opioid infusion versus bolus administration of opioids was evaluated in six studies, while one study compared 'as needed' versus 'as scheduled' administration of morphine given by parents or nurses. Overall, the effectiveness of continuous infusion of opioids over bolus infusion as measured by the visual analog scale (MD 0.00, 95% confidence interval (CI) -0.23 to 0.23; 133 participants, 2 studies; I² = 0); or using the COMFORT scale (MD -0.07, 95% CI -0.89 to 0.75; 133 participants, 2 studies; I² = 0), remains unclear due to study designs' limitations, such as the unclear risk of attrition, reporting bias, and imprecision among reported results (very low certainty of the evidence). None of the included studies reported data on other clinically important outcomes such as all-cause mortality rate during hospitalization, major neurodevelopmental disability, the incidence of severe retinopathy of prematurity or intraventricular hemorrhage, and cognitive- and educational-related outcomes. AUTHORS' CONCLUSIONS: Limited evidence is available on continuous infusion compared to intermittent boluses of systemic opioids. We are uncertain whether continuous opioid infusion reduces pain compared with intermittent opioid boluses; none of the studies reported the other primary outcomes of this review, i.e. all-cause mortality during initial hospitalization, significant neurodevelopmental disability, or cognitive and educational outcomes among children older than five years old. Only one small study reported on morphine infusion with parent- or nurse-controlled analgesia.
Topics: Humans; Infant, Newborn; Analgesia; Analgesics, Opioid; Clinical Protocols; Morphine; Pain, Postoperative
PubMed: 36645224
DOI: 10.1002/14651858.CD015016.pub2 -
BMJ Case Reports Jan 2020Terlipressin is a commonly used drug in hepatology practice for the two most serious complications of cirrhosis, that is, acute oesophageal variceal bleed and...
Terlipressin is a commonly used drug in hepatology practice for the two most serious complications of cirrhosis, that is, acute oesophageal variceal bleed and hepatorenal syndrome. Acute-on-chronic liver failure (ACLF) is a medical emergency and is frequently associated with acute kidney injury (AKI). Two male patients with alcohol-induced ACLF with high MELD (Model for End-Stage Liver Disease) score presented with AKI. Both were treated with terlipressin infusion. There was no response to terlipressin in these sick patients, and further both patients developed ischaemic skin necrosis and succumbed to multiorgan failure. Continuous infusion of terlipressin is superior to bolus dosing, but we noted that continuous infusion might as well be associated with severe adverse effects in patients with a high MELD score. More extensive prospective studies, including patients with high MELD score, are required to ascertain the safety of terlipressin.
Topics: Acute Kidney Injury; Acute-On-Chronic Liver Failure; Diagnosis, Differential; Humans; Ischemia; Male; Middle Aged; Necrosis; Skin Diseases; Terlipressin
PubMed: 31948983
DOI: 10.1136/bcr-2019-233089 -
Drug Metabolism and Disposition: the... Sep 2020Blood and multitissue concentration-time profiles for dexamethasone (DEX), a synthetic corticosteroid, were measured in male rats after subcutaneous bolus and infusion...
Blood and multitissue concentration-time profiles for dexamethasone (DEX), a synthetic corticosteroid, were measured in male rats after subcutaneous bolus and infusion dosing. A physiologically based pharmacokinetics (PBPK) model was applied for 12 measured tissues. Tissue partition coefficients ( ) and metabolic clearance were assessed from infusion studies. Blood cell to plasma partitioning (0.664) and plasma free fraction (0.175) for DEX were found to be moderate. DEX was extensively partitioned into liver ( = 6.76), whereas the calculated values of most tissues ranged between 0.1 and 1.5. Despite the moderate lipophilicity of DEX (log = 1.8), adipose exhibited very limited distribution ( = 0.17). Presumably due to P-glycoprotein-mediated efflux, DEX concentrations were very low in brain compared with its expected high permeability. Infusion studies yielded values from male and female rats at steady state that were similar. In silico values calculated for different tissues by using GastroPlus software were similar to in vivo values except for adipose and liver. Glucocorticoid receptors are found in diverse tissues, and these PBPK modeling results may help provide exposure profiles driving pharmacodynamic effects of DEX. SIGNIFICANCE STATEMENT: Our physiologically based pharmacokinetics model describes the experimentally determined tissue and plasma dexamethasone (DEX) pharmacokinetics (PK) profiles in rats reasonably well. This model can serve for further investigation of DEX tissue distribution in rats as the PK driving force for PD effects in different tissues. No major sex differences were found for DEX tissue distribution. Knowledge gained in this study may be translatable to higher-order species including humans.
Topics: ATP Binding Cassette Transporter, Subfamily B; Animals; Computer Simulation; Dexamethasone; Drug Evaluation, Preclinical; Female; Glucocorticoids; Infusions, Subcutaneous; Male; Models, Animal; Models, Biological; Rats; Sex Factors; Tissue Distribution
PubMed: 32601175
DOI: 10.1124/dmd.120.091017 -
British Journal of Anaesthesia Aug 2022Intravenous lidocaine has been postulated to improve long-term survival after surgery for pancreatic cancer through anti-inflammatory effects, anti-tumour effects, or... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Intravenous lidocaine has been postulated to improve long-term survival after surgery for pancreatic cancer through anti-inflammatory effects, anti-tumour effects, or both. We investigated whether intraoperative lidocaine improves survival after pancreatectomy for pancreatic cancer and whether lidocaine modified the formation of neutrophil extracellular traps (NETs), high levels of which are associated with poor prognosis.
METHODS
Patients undergoing pancreatectomy were randomly assigned to i.v. lidocaine (continuous intraoperative infusion of 2 mg kg h, after 1.5 mg kg bolus at induction of anaesthesia) or saline placebo. The co-primary outcomes were survival/disease-free survival 3 yr after surgery. Secondary outcomes (masked to treatment allocation) included intraoperative opioid (sufentanil) dose, postoperative complications, and circulating and tumour-associated NETs (immunofluorescence assay, enzyme-linked immune assay, or both).
RESULTS
A total of 563 participants (34.6% female; median age, 64 yr) completed 3 yr of clinical follow-up. Overall, 283 participants were randomised to lidocaine infusion, and 280 participants were randomised to placebo. Infusion of lidocaine did not alter overall (hazard ratio [HR]=0.98; 95% confidence interval [CI], 0.81-1.17; P=0.79) or disease-free survival (HR=0.91; 95% CI, 0.71-1.17; P=0.44). Mean intraoperative sufentanil dose was reduced by lidocaine infusion (47.6 μg [4.6]) compared with placebo (68.4 μg [4.8]; P<0.001), but postoperative complications and length of hospital stay were similar between groups. Circulating NETs were lower after lidocaine infusion up to 3 days after surgery, but tumour-associated NETs were not altered by intraoperative treatment.
CONCLUSION
In patients undergoing pancreatectomy for pancreatic cancer, intraoperative infusion of lidocaine did not improve overall or disease-free survival. Reduced formation of circulating NETs was absent in pancreatic tumour tissue.
CLINICAL TRIAL REGISTRATION
NCT03245346; updated in Chi-CTR-2000035469.
Topics: Anesthetics, Local; Double-Blind Method; Female; Humans; Infusions, Intravenous; Lidocaine; Male; Middle Aged; Pain, Postoperative; Pancreatectomy; Pancreatic Neoplasms; Postoperative Complications; Sufentanil
PubMed: 35697547
DOI: 10.1016/j.bja.2022.03.031 -
Pain Research & Management 2022Despite the clinical effectiveness of the programmed intermittent bolus (PIB) method for epidural analgesia, evidence for this method in continuous interscalene brachial...
Comparison of Continuous and Programmed Intermittent Bolus Infusion of 0.2% Ropivacaine after Ultrasound-Guided Continuous Interscalene Brachial Plexus Block in Arthroscopic Shoulder Surgery.
BACKGROUND
Despite the clinical effectiveness of the programmed intermittent bolus (PIB) method for epidural analgesia, evidence for this method in continuous interscalene brachial plexus block (CIBPB) is unclear. This study aimed to investigate the pain relief effect after arthroscopic shoulder surgery according to the administration method by comparing the PIB and continuous infusion methods among the administration methods of local anesthetics.
METHODS
Sixty-four patients aged >19 years scheduled for elective arthroscopic shoulder surgery were enrolled and divided into two groups. Ultrasound-guided CIBPB was performed to control postoperative pain. The infusion pump was programmed so that 0.2% ropivacaine was continuously injected at 1.1 mL/h in group A, whereas in group B, 0.1 mL/h was continuously injected and 4 mL was periodically injected at 4 h intervals. In both groups, a further infusion of 4 mL of 0.2% ropivacaine was administered if the patient requested additional analgesia, and the lockout time was set at 30 min. Postoperative pain quality was assessed using a visual analog scale (VAS), and the incidence of patients requiring additional analgesics, motor blockade using a modified Bromage scale (MBS), and consumed doses of local anesthetic were assessed.
RESULTS
The VAS and incidence of rescue analgesics were performed when the patient could communicate voluntarily after admission to the post-anesthetic care unit, and at 24 and 48 h after surgery showed no significant difference between the two groups. The MBS at 24 h after surgery was significantly higher in group B ( = 0.038). In the comparison of consumed doses of local anesthetic, group B had a significantly higher bolus injection dose ( = 0.047) and frequency of bolus use in the 24 h after surgery ( = 0.034).
CONCLUSION
The PIB method in CIBPB after arthroscopic shoulder surgery provided a similar analgesic effect, with a higher bolus injection dose of local anesthetic and increased motor blockade than the continuous infusion method.
Topics: Humans; Ropivacaine; Anesthetics, Local; Brachial Plexus Block; Shoulder; Amides; Pain, Postoperative; Analgesics; Ultrasonography, Interventional; Double-Blind Method
PubMed: 36601435
DOI: 10.1155/2022/2010224 -
Canadian Journal of Pain = Revue... 2023Craniofacial pain (CFP) poses a burden on patients and health care systems. It is hypothesized that ketamine, an -methyl-d-aspartate (NMDA) receptor antagonist, can... (Review)
Review
BACKGROUND
Craniofacial pain (CFP) poses a burden on patients and health care systems. It is hypothesized that ketamine, an -methyl-d-aspartate (NMDA) receptor antagonist, can reverse central sensitization associated with causation and propagation of CFP. This systematic review aims to assess the role of ketamine for CFP.
METHODS
Databases were searched for studies published up to September 26, 2022, investigating the efficacy of ketamine for adults with CFP. Primary outcome was the change in pain intensity at 60 min postintervention. Two reviewers screened and extracted data. Registration with PROSPERO was performed (CRD42020178649).
RESULTS
Twenty papers (six randomized controlled trials [RCTs], 14 observational studies) including 670 patients were identified. Substantial heterogeneity in terms of study design, population, dose, route of administration, treatment duration, and follow-up was noted. Bolus dose ranged from 0.2-0.3 mg/kg (intravenous) to 0.4 mg/kg (intramuscular) to 0.25-0.75 mg/kg (intranasal). Ketamine infusions (0.1-1 mg/kg/h) were given over various durations. Follow-up was short in RCTs (from 60 min to 72 h) but longer in observational studies (up to 18 months). Ketamine by bolus treatment failed to reduce migraine intensity but had an effect by reducing intensity of aura, cluster headache (CH), and trigeminal neuralgia. Prolonged ketamine infusions showed sustainable reduction of migraine intensity and frequency of CH attacks, but the quality of the evidence is low.
CONCLUSION
Current evidence remains conflicting on the efficacy of ketamine for CFP owing to low quality and heterogeneity across studies. Ketamine infusions are suggested to provide sustained improvement, possibly because of prolonged duration and higher dosage of administration. RCTs should focus on the dose-response relationship of prolonged ketamine infusions on CFP.
PubMed: 37383673
DOI: 10.1080/24740527.2023.2210167 -
Journal of Aerosol Medicine and... Jan 2022A new real-time method for assessing factors determining aerosol delivery is described. A breath-enhanced jet nebulizer operated in a ventilator/heated humidifier...
A new real-time method for assessing factors determining aerosol delivery is described. A breath-enhanced jet nebulizer operated in a ventilator/heated humidifier system was tested during bolus and continuous infusion aerosol delivery. Tc (technetium)/saline was either injected (3 or 6 mL) or infused over time into the nebulizer. A shielded gamma ratemeter was oriented to count radioaerosol accumulating on an inhaled mass (IM) filter at the airway opening of a test lung. Radioactivity measured at 2-10-minute intervals was expressed as % nebulizer charge (bolus) or % syringe activity per minute infused. All circuit parts were measured and imaged by gamma camera to determine mass balance. Ratemeter activity quantitatively reflected immediate changes in IM: 3 and 6 mL bolus IM% = 16.1 and 18.8% in 6 and 14 minutes, respectively; infusion IM% = 0.64 + 0.13 (run time, min), 0.999. Effect of nebulizer priming and system anomalies were readily detected in real time. Mass balance (basis = dose infused in 90 minutes): IM 39.2%, breath-enhanced jet nebulizer residual 35.5%, circuit parts including humidifier 23.4%, and total recovery 98.1%. Visual analysis of circuit component images identified sites of increased deposition. Real-time ratemeter measurement with gamma camera imaging provides operational feedback during testing procedures and yields a detailed analysis of the parameters influencing drug delivery during mechanical ventilation. This method of analysis facilitates assessment of device function and influence of circuit parameters on drug delivery.
Topics: Administration, Inhalation; Aerosols; Albuterol; Bronchodilator Agents; Drug Delivery Systems; Equipment Design; Nebulizers and Vaporizers; Respiration, Artificial
PubMed: 34227873
DOI: 10.1089/jamp.2021.0019