"Inactive" ingredients in oral medications Reker, Daniel; Blum, Steven M; Steiger, Christoph ...
Science translational medicine,
03/2019, Volume:
11, Issue:
483
Journal Article
Peer reviewed
Open access
Oral forms of medications contain "inactive" ingredients to enhance their physical properties. Using data analytics, we characterized the abundance and complexity of inactive ingredients in approved ...medications. A majority of medications contain ingredients that could cause adverse reactions, underscoring the need to maximize the tolerability and safety of medications and their inactive ingredients.
Management of pain, agitation, and delirium is a complex process requiring a multimodal approach to optimize patient outcomes. Dexmedetomidine is a centrally acting alpha-2 agonist with sedative and ...analgesic properties that has demonstrated efficacy in managing pain, agitation, and delirium in a variety of critically ill patient populations. Dexmedetomidine has demonstrated the ability to provide a mild to moderate level of sedation in diverse ICU populations compared to conventional sedative regimens. Recent literature has demonstrated improved outcomes with dexmedetomidine based vs. benzodiazepine based sedation therapy in select mechanically ventilated ICU patients. However, dexmedetomidine therapy has also been associated with adverse cardiovascular events including hypotension, bradycardia, and asystole. The clinical pharmacology, therapeutic efficacy, safety considerations, controversies, and future directions of dexmedetomidine therapy in the ICU setting will be discussed.
Medication administration via intravenous push presents multiple potential advantages; however, there may be an increased risk of adverse drug reactions. In 2020, Brigham and Women's Hospital changed ...levetiracetam intravenous administration to intravenous push (IVP).
The purpose of this analysis was to compare the safety profile of IVP to intravenous piggyback (IVPB) levetiracetam administration.
This institutional review board-approved, single-center, pre-post analysis was performed between 1 November, 2019 and 30 May, 2020. The electronic health record was used to identify all administrations of intravenous levetiracetam greater than 1000 mg in patients ≥ 18 years old. The major safety outcomes included hypotension, bradycardia, drug-induced sedation, and intravenous site reactions such as phlebitis and infiltration. The major efficiency outcome was the time from pharmacy order verification to first-dose administration.
A total of 498 administrations in 162 patients were included in the analysis: 252 administrations in 84 patients in the IVP group and 246 administrations in 78 patients in the IVPB group. The incidence of bradycardia was 7 vs 3 (3.2% vs 1.5%, p = 0.34); hypotension 10 vs 6 (5.2% vs 3.5%, p = 0.44); sedation 21 vs 36 (19.3% vs 27.9%, p = 0.12); and peripheral IV site reactions 0 vs 1 (0% vs 0.6%, p = 0.39) in the IVP vs IVPB groups, respectively. The median time between order verification and first-dose administration was significantly reduced in the IVP vs IVPB group (23.5 vs 55 min, p < 0.001).
Intravenous push levetiracetam administration of doses up to 4000 mg was associated with a similar incidence of cardiovascular, sedation, and infusion site-related adverse events compared to IVPB and resulted in a significant reduction in time to first-dose administration. Intravenous push levetiracetam in doses as high as 4000 mg may be considered safe with appropriate monitoring.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Background:
There are limited data regarding the incidence of adverse events associated with administering lacosamide by intravenous push (IVP) compared with IV piggyback (IVPB).
Objective:
The ...objective of this analysis was to compare the safety profile, including cardiovascular effects, sedative effects, and IV site reactions of IVP and IVPB lacosamide administration.
Methods:
A retrospective pre/post cohort analysis comparing patients who received lacosamide via IVP and IVPB was conducted. Safety end points included hypotension, bradycardia, medication-related sedation, and IV site reactions. The relationship between patient characteristics and the incidence of safety end points was analyzed using the Student t-test and χ2 test as appropriate.
Results:
Bradycardia occurred after 0.19% of IVP administrations and 1.09% of IVPB administrations assessed (P = 0.07). Hypotension was observed in 3.16% of IVP administrations compared to 1.59% in the IVPB cohort (P = 0.12). Post lacosamide-related sedation was noted in 11.32% and 11.68% of the IVP and IVPB cohorts, respectively (P = 0.87). Infusion site reaction rates of 1.80% and 0.84% were documented in the IVP and IVPB cohorts, respectively (P = 0.33). Of note, only 1 adverse event required clinical intervention. One 200-mg dose in the IVP cohort required a fluid bolus postadministration.
Conclusion and Relevance:
IVP lacosamide was associated with a similar incidence of cardiovascular, neurological, and infusion site–related adverse events compared with IVPB, in which nearly every adverse event was deemed clinically insignificant. Lacosamide administered via IVP may be considered a safe alternative method of administration in the acute care setting.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
While propofol is associated with an infusion syndrome (PRIS) that may cause death, the incidence of PRIS is unknown. Determining the incidence of PRIS and the frequency of PRIS-related clinical ...manifestations are key steps prior to the completion of any controlled studies investigating PRIS. This prospective, multicenter study sought to determine the incidence of PRIS and PRIS-related clinical manifestations in a large cohort of critically ill adults prescribed propofol.
Critically ill adults from 11 academic medical centers administered an infusion of propofol for >or= 24 hours were monitored at baseline and then on a daily basis until propofol was discontinued for the presence of 11 different PRIS-associated clinical manifestations and risk factors derived from 83 published case reports of PRIS.
Among 1017 patients medical (35%), neurosurgical (25%), PRIS (defined as metabolic acidosis plus cardiac dysfunction and >or= 1 of: rhabdomyolysis, hypertriglyceridemia or renal failure occurring after the start of propofol therapy) developed in 11 (1.1%) patients an average of 3 (1-6) median (range) days after the start of propofol. While most (91%) of the patients who developed PRIS were receiving a vasopressor (80% initiated after the start of propofol therapy), few received a propofol dose >83 mcg/kg/min (18%) or died (18%). Compared to the 1006 patients who did not develop PRIS, the APACHE II score (25 +/- 6 vs 20 +/- 7, P = 0.01) was greater in patients with PRIS but both the duration of propofol use (P = 0.43) and ICU length of stay (P = 0.82) were similar.
Despite using a conservative definition for PRIS, and only considering new-onset PRIS clinical manifestations, the incidence of PRIS slightly exceeds 1%. Future controlled studies focusing on evaluating whether propofol manifests the derangements of critical illness more frequently than other sedatives will need to be large. These studies should also investigate the mechanism(s) and risk factors for PRIS.
Abstract Purpose The purpose of this is to compare efficacy, safety, and cost outcomes in patients who have received either inhaled epoprostenol (iEPO) or inhaled nitric oxide (iNO) for hypoxic ...respiratory failure. Materials and methods This is a retrospective, single-center analysis of adult, mechanically ventilated patients receiving iNO or iEPO for improvement in oxygenation. Results We evaluated 105 mechanically ventilated patients who received iEPO (52 patients) or iNO (53 patients) between January 2009 and October 2010. Most patients received therapy for acute respiratory distress syndrome (iNO 58.5% vs iEPO 61.5%; P = .84). There was no difference in the change in the partial pressure of arterial O2 /fraction of inspired O2 ratio after 1 hour of therapy (20.58 ± 91.54 vs 33.04 ± 36.19 P = .36) in the iNO and iEPO groups, respectively. No difference was observed in duration of therapy ( P = .63), mechanical ventilation ( P = .07), intensive care unit ( P = .67), and hospital lengths of stay ( P = .26) comparing the iNO and iEPO groups. No adverse events were attributed to either therapy. Inhaled nitric oxide was 4.5 to 17 times more expensive than iEPO depending on contract pricing. Conclusions We found no difference in efficacy and safety outcomes when comparing iNO and iEPO in hypoxic, critically ill patients. Inhaled epoprostenol is associated with less drug expenditure than iNO.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Abstract Purpose The objective of this study was to evaluate the use of sedative, analgesic, and neuromuscular blocking agents (NMBAs) in patients undergoing ECMO support. Materials and methods This ...was a two year, prospective, observational study of adult ICU patients on ECMO support for more than 48 hours. Results We analyzed 32 patients, including 15 VA ECMO and 17 VV ECMO. The median daily dose of benzodiazepines (midazolam equivalents) was 24 mg and the median daily dose of opioids (fentanyl equivalents) was 3875 mcg. There was a moderate negative correlation between the day of ECMO and the median daily benzodiazepine dose (r = −0.5515) and a very weak negative correlation for the median daily opioid dose (r = −0.0053). On average patients were sedated to RASS scores between 0 and −1. Continuous infusions of opioids, benzodiazepines, propofol, dexmedetomidine, and neuromuscular blocking agents were administered on 404 (85.1%), 199 (41.9%), 95 (20%), 32 (6.7%), and 60 (12.6%) ECMO days, respectively. Patients in the VA arm received a continuous infusion opioid (96.4% vs. 81.6% days, P < .001) and benzodiazepine (58.2% vs. 37.0% days, P < .001) more frequently. Conclusions Patients received relatively low doses of sedatives and analgesics while at a light level of sedation on average. Patients rarely required neuromuscular blockade.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Background: Recent shortages of intravenous (IV) fluids have resulted in healthcare systems converting administration of many medications from IV piggyback (IVPB) to IV push (IVP). Administering ...medications via IVP presents numerous advantages; however, IV site reactions such as phlebitis and infiltration may occur. Objective: The objective of this analysis is to evaluate the infusion site safety of ertapenem given as peripheral IVP compared to IVPB in adult patients. Methods: This was an institutional review board–approved, single-center, retrospective study. Patients, ages 18 or older, receiving IV ertapenem were identified. The major endpoints analyzed were IV site reactions including phlebitis and infiltration. The Naranjo Nomogram was utilized to assess the causality of the reactions to determine the likelihood of whether the event was caused by the medication itself or other factors. Results: To date, 283 administrations (92 patients) in the IVP group and 319 administrations (82 patients) in the IVPB group were analyzed. There were 13 IV site reactions compared to 8 in the IVP vs IVPB group, respectively (P-value = 0.16). Ten of the events in the IVP group were deemed “possible” and 2 deemed “doubtful,” while the remaining event was considered “probable” per the Naranjo Nomogram. Of the events in the IVPB group, all 8 were found to be “possible.” Conclusion: The administration of IVP ertapenem showed comparable rates of infusion site reactions compared to IVPB. Implementation of IVP ertapenem appears to be associated with infusion site safety similar to IVPB and should be considered safe to administer.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK, VSZLJ
Antiepileptics used for seizure prophylaxis after traumatic brain injury (TBI) are reviewed.
Of the 275,000 people who are hospitalized with TBI each year, approximately 5-7% experience a ...posttraumatic seizure (PTS). According to the latest guidelines issued by the Brain Trauma Foundation and the American Academy of Neurology (AAN) for the management of severe TBI, PTS prophylaxis is recommended only during the first seven days after TBI. Of the available antiepileptic drugs, phenytoin has been the most extensively studied for the prophylaxis of PTS. Phenobarbital, valproate, and carbamazepine have not been as extensively researched, and, given their adverse-effect profiles and pharmacodynamic properties, there is no advantage to using these agents over phenytoin. Levetiracetam has demonstrated comparable efficacy to phenytoin for PTS prophylaxis and is associated with fewer adverse effects and monitoring considerations; it may be a reasonable alternative to phenytoin. However, levetiracetam has been associated with an increased seizure tendency. The Brain Trauma Foundation recommends using phenytoin for early PTS prophylaxis. The guidelines also state that valproate has demonstrated similar efficacy to phenytoin but warn that its use may be associated with increased mortality.
The available literature supports the use of antiepileptics for early PTS prophylaxis during the first week after a TBI. Phenytoin has been extensively studied for this indication and is recommended by the AAN and Brain Trauma Foundation guidelines for early PTS prophylaxis. Levetiracetam has demonstrated comparable efficacy to phenytoin for early PTS prophylaxis and may be a reasonable alternative to consider in this patient population.
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DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
The optimal monitoring strategy for anticoagulation management in extracorporeal membrane oxygenation (ECMO) remains a clinical controversy. The Extracorporeal Life Support Organization ...Anticoagulation Guidelines suggest that multiple anticoagulation assays may be needed but do not specify a preferred management strategy.
In adult ECMO patients, which anticoagulation assays demonstrate the highest correlation with unfractionated heparin (UFH) dose requirements?
We performed a retrospective chart review of adult patients cannulated to ECMO between February 2013 and July 2015.
The primary outcome was the correlation between activated clotting time (ACT), activated partial thromboplastin time (aPTT), and anti-Xa and UFH dose. Secondary outcomes included correlations between anticoagulation assays. Correlations were calculated for the entire cohort, with subgroup analysis of venoarterial and venovenous ECMO patients.
Forty-eight patients were included in the analysis, 26 initially cannulated to venoarterial ECMO and 22 to veno-venous ECMO. The median duration of ECMO therapy was 7 days. Mean UFH requirements were 1149 units/h or 15.3 units/kg/h. Total UFH dose was most correlated with anti-Xa levels (r = 0.467), whereas weight-based heparin dose was most correlated with aPTT (0.405). For correlations between anticoagulation assays, anti-Xa and aPTT were more highly correlated with each other (r = 0.633) compared with ACT.
In adult patients requiring ECMO, anti-Xa and aPTT monitoring were correlated more closely with UFH dosing than ACT.
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