To review the efficacy and safety of transitioning from dexmedetomidine to clonidine to facilitate weaning of patients from sedation with dexmedetomidine. There is a paucity of data describing ...dexmedetomidine withdrawal syndrome (DWS) as well as clonidine's place in therapy for DWS. This review will describe and analyze current literature to provide clinical recommendations.
A MEDLINE literature search was performed to identify original research articles describing DWS and/or transitioning from dexmedetomidine to clonidine for the purpose of weaning patients from sedation with dexmedetomidine. Four case reports describing DWS, 3 case reports describing the use of clonidine to treat DWS, and 3 observational studies describing the use of clonidine to facilitate dexmedetomidine weaning were identified. The incidence of and risk factors for DWS are unknown; factors including patient age and dexmedetomidine infusion rate, loading dose, and discontinuation strategy have inconsistent associations with DWS. All cases of DWS have been associated with infusion durations greater than 72 hours. While there are limited data describing clonidine use for the treatment of dexmedetomidine withdrawal, clonidine appears to be beneficial for dexmedetomidine weaning and its use for that purpose has been well described. Clonidine dosages that have been assessed for discontinuing dexmedetomidine vary from 0.1 to 0.3 mg orally or enterally every 6 to 8 hours; one study assessed use of transdermal clonidine (100 µg/24 h patch). Patients with extensive cardiac comorbidities may be more susceptible to adverse effects of clonidine, which may limit the drug's use for DWS intervention.
Despite limited supportive data, clonidine provides a promising option for sedation management in adult ICU patients, with successful transitions from dexmedetomidine reported within 24 hours after clonidine initiation.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Purpose:
To compare clinical response of intermittent bolus versus continuous infusion neostigmine for acute colonic pseudo-obstruction (ACPO). Acute colonic pseudo-obstruction occurs due to reduced ...colonic parasympathetic activity. Neostigmine is an acetylcholinesterase inhibitor that increases frequency of smooth muscle contraction by increasing acetylcholine at autonomic nervous system synapses. Although these administration modalities have been studied separately, they have never been compared.
Methods:
This retrospective study compared bolus versus continuous infusion neostigmine for ACPO. The primary outcome was initial clinical response, defined as bowel movement (BM) within 4 hours of bolus dose or 24 hours of initiation of continuous infusion. Secondary outcomes included time to BM, bowel diameter reduction at 24 hours, incidence of bradycardia, additional neostigmine requirements, and need for colonic decompression or surgical intervention.
Results:
Seventy-five patients were included (bolus n = 37; infusion n = 38). Median total 24-hour neostigmine dose was 2.0 mg (interquartile range IQR: 2.0-2.6) with bolus and 9.6 mg (IQR: 6.3-9.6) with continuous infusion. Initial clinical response was similar (infusion 81.6% vs bolus 62.2%, P = .06), but continuous infusion was associated with greater bowel diameter reduction (73.7% vs 40.5%, P = .004). Bolus administration had shorter time to BM (1.4 vs 3.5 hours, P = .0478) and increased need for colonic decompression (67.6% vs 39.5%, P = .0148). Bolus dosing was associated with less bradycardia (13.5% vs 39.5%, P = 0.011), with no difference in atropine usage (10.8% vs 5.3%, P = .43).
Conclusion:
Initial clinical response was similar between groups; however, continuous infusion neostigmine was associated with greater bowel diameter reduction at 24 hours. Bolus administration resulted in less bradycardia; however, given the lack of difference in atropine use, clinical significance is unknown. This study is the first to compare bolus versus continuous infusion neostigmine for ACPO. Further studies are needed to confirm findings.
Background:
Trials evaluating hydrocortisone (HC) for septic shock are conflicting with all finding decreased time to shock reversal but few with mortality difference. Those with improved mortality ...included fludrocortisone (FC), but it is unknown if FC affected the outcome or is coincidental as there are no comparative data.
Objective:
The objective of this study was to determine the effectiveness and safety of FC + HC versus HC alone as adjunctive therapy in septic shock.
Methods:
A single-center, retrospective cohort study was conducted of medical intensive care unit (ICU) patients with septic shock refractory to fluids and vasopressors. Patients receiving FC + HC were compared with those receiving HC. Primary outcome was time to shock reversal. Secondary outcomes included in-hospital, 28-, and 90-day mortality; ICU and hospital length of stay (LOS); and safety.
Results:
There were 251 patients included (FC + HC, n = 114 vs HC, n = 137). There was no difference in time to shock reversal (65.2 vs 71 hours; P = 0.24). Cox proportional hazards model showed time to first corticosteroid dose, full-dose HC duration, and use of FC + HC were associated with shorter shock duration, while time to vasopressor therapy was not. However, in 2 multivariable models controlling for covariates, use of FC + HC was not an independent predictor of shock reversal at greater than 72 hours and in-hospital mortality. No differences were seen in hospital LOS or mortality. Hyperglycemia occurred more frequently with FC + HC (62.3% vs 45.6%; P = 0.01).
Conclusion and Relevance:
FC + HC was not associated with shock reversal at greater than 72 hours or decreased in-hospital mortality. These data may be useful for determining corticosteroid regimen in patients with septic shock refractory to fluids and vasopressors. Future prospective, randomized studies are needed to further evaluate the role of FC in this patient population.
Introduction: Calcium channel blockers (CCB) are a leading cause of ingestion-associated fatality. Angiotensin-converting enzyme inhibitor (ACEi) overdose as part of co-ingestion is common and ...associated with refractory shock. Treatment options to manage this profound vasoplegia are limited. We describe the first case of use of newly formulated Angiotensin II for treatment of severe ACEi and CCB poisoning. Case Report: A 57-year-old man presented after suicide attempt by ingesting 20 tablets each of amlodipine 10 mg and benazepril 20 mg. His hypotension was initially managed with 35 mL/kg of crystalloid, norepinephrine, and hyperinsulinemic euglycemic therapy (HIET). His hemodynamics further deteriorated, and he developed lactic acidosis, electrolyte derangements, and renal dysfunction. Further complications of his ingestion included cardiac arrest, subsequent requirement for emergency cricothyrotomy, and renal replacement therapy. Maximal hemodynamic support with HIET therapy insulin drip 4.4 units/kg/hour, norepinephrine 2 mcg/kg/min, epinephrine 1 mcg/kg/min, vasopressin .06 units/hour, and intravenous lipid emulsion was unsuccessful. Ang II was started and titrated to maximal doses with dramatic improvement in hemodynamics. Within hours of starting Ang II, epinephrine was stopped and norepinephrine decreased by 50%. He was downgraded from the intensive care unit without any ongoing end-organ dysfunction. Discussion: Isolated CCB overdoses have high complication rates and well-established treatments. Therefore, management of CCB and ACEi co-ingestion is typically driven by CCB poisoning algorithm. There are multiple reports of CCB and ACEi co-ingestions causing treatment-refractory shock. Therapeutic options are limited by toxicities and availability of salvage therapies. Ang II is a safe and highly effective option to manage these patients.
Background:
Ketamine, an N-methyl-d-aspartate receptor antagonist with sedative and analgesic properties, is becoming more popular as an adjunctive sedative in the critically ill patients.
Methods:
...We conducted a single center, retrospective cohort study of patients admitted to the medical intensive care unit (MICU) between 2013 and 2018. Patients who received continuous infusion ketamine or nonketamine sedatives (NKS) including dexmedetomidine, fentanyl, midazolam, or propofol were identified. The primary outcome was percentage of Richmond Agitation-Sedation Scale (RASS) scores at goal in patients receiving ketamine as adjunct to NKS compared to those on NKS alone.
Results:
A total of 172 patients were included (n = 86 ketamine, n = 86 NKS). Baseline characteristics were similar with the exception of antipsychotic use, which was higher in the ketamine group (P = .008). Percentage of RASS scores at goal was not different between groups (78.7% vs 81.4%, P = .29). Fewer patients in the ketamine group received continuous infusion fentanyl (76.7% vs 94.2%, P = .002). Patients on adjunctive ketamine required fewer days of intermittent benzodiazepines (0 0-1 vs 1 1-2, P < .0001). Patients receiving ketamine required less norepinephrine, receiving a median of 6.32 mg (2.4-20) versus 11.7 mg (5.2-45.2; P = .03). There was no difference in receipt of new antipsychotics or occurrence of arrhythmias.
Conclusion:
Addition of ketamine did not increase the percentage of RASS scores at goal versus NKS but was well tolerated. Ketamine was associated with reductions in norepinephrine requirements, days of intermittent benzodiazepine administration, and number of patients receiving continuous infusion fentanyl. Continuous infusion ketamine appears safe and effective for sedation in the MICU.
Background:
Corticosteroids (CSs), specifically dexamethasone (DEX), are the treatment of choice for severe acute respiratory distress syndrome (ARDS) due to COVID-19 pneumonia (CARDS). However, data ...from both ARDS and relatively small CARDS clinical trials have suggested improved outcomes with methylprednisolone (MP) versus DEX. The objective of this retrospective cohort study was to compare the safety and effectiveness of MP and DEX in critically ill CARDS patients.
Methods:
The study cohort included CARDS patients admitted to a tertiary referral intensive care unit (ICU) between April and September 2020 who received at least 5 days of CSs for CARDS.
Results:
The cohort was notable for a high severity of illness (overall, 88.5% of patients required mechanical ventilation and 16% required vasopressors on admission). The DEX group (n = 62) was significantly older with a higher illness severity Sequential Organ Failure Assessment (SOFA) 6 (4.75–8) versus 4.5 (3–7), p = 0.008, while the MP group (n = 51) received significantly more loading doses 19 (37.3%) versus 4 (6.5%), p < 0.0001. MP was associated with a shorter time to intubation and more rapid progression to mortality days to death: 18 (15–23) versus 27 (15–34), p = 0.026. After correction for baseline imbalances in age and SOFA score, DEX was associated with improved mortality at 90 days compared with MP hazard ratio (HR) = 0.43, 95% confidence interval (CI) = 0.23–0.80, p = 0.008. However, there were no differences between rates of secondary infections during hospitalization or insulin requirements at 7 and 14 days.
Conclusion:
In this cohort of critically ill CARDS, choice of CS was associated with mortality but not adverse event profile, and thus warrants further investigation.
Hospitalized patients with SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) are at risk for developing secondary fungal infections due to greater incidence of preexisting comorbidities ...and exposure to iatrogenic factors such as corticosteroid use. We present the case of a 44-year-old Hispanic female discovered unresponsive in her home that was found to have severe hyperglycemia with comorbid COVID-19 (coronavirus disease 2019) associated pneumonia. The patient was intubated and treated with several broad-spectrum antibiotics, remdesivir, and corticosteroids but had little improvement in her clinical status. Bronchoscopy was performed and revealed multiple necrotic lesions in the lungs. Endobronchial biopsy and bronchoalveolar lavage samples revealed pauciseptated hyphae consistent with zygomycetes. The patient was treated with multiple antifungals including voriconazole, micafungin, and amphotericin B. However, despite maximal medical therapy, the patient perished. This case highlights that clinicians must carry a high degree of suspicion and a low threshold to begin treatment for Mucor in diabetics and other immunosuppressed patients. Keywords: SARS-CoV-2; COVID-19; mucormycisis; diabetes melitus; thoracic CT; remdesivir
Abstract
Background
Mucormycosis is a rare and aggressive mold infection with an all-cause mortality of 54%. Treatment for mucormycosis has historically consisted of high dose liposomal amphotericin ...B (LAmB) as monotherapy. Recent data has emerged studying combination therapies; however, this data is conflicting, and the benefit of combination therapy remains unclear. This case series aims to explore different combination therapies utilized for the treatment of mucormycosis and their effect on mortality.
Methods
We report 17 cases of proven or probable mucormycosis managed with combination therapy for at least 48 hours at University Hospital between March 2020 and November 2022.
Results
The median age of patients was 60 years old (range 21-74), and 11 patients were male (64.7%), with a median BMI of 27.8 kg/m2. Of the 17 patients, all patients (100%) were Hispanic, nine patients (53%) had diabetes and two patients (12%) were lung transplant recipients. The most common infection site was rhino-orbital (6/17; 35%) and surgery was performed on 11 patients (64.7%) after a median of two days after hospital admission. All 17 patients received LAmB with an average initial dose of 5.13 mg/kg/day (range 2.9-6.4 mg/kg/day). All patients received combination therapy with either posaconazole (6/17; 35.2%), micafungin (4/17; 23.5%), or triple therapy (7/17; 41.2%). Duration of combination therapy was a median six days (range 2-21 days). Five of the 17 patients (29%) died of mucormycosis-related complications. Mortality observed in patients receiving combination therapy is as follows: micafungin combination (4/4; 100%), posaconazole combination (5/6; 83%), and triple therapy (0/7; 0%).
Conclusion
Mucormycosis is an aggressive fungal infection with high morbidity and mortality that requires immediate recognition, urgent intervention, and appropriate antifungal dosing. Combination therapy with micafungin maybe associated with higher mortality compared to posaconazole or triple therapy. In this cohort, combination may be associated with lower mortality that previously documented but further investigation is required to determine optimal combination treatment for invasive mucormycosis.
Disclosures
Kelly Reveles, PharmD, PhD, Ferring Pharmaceuticals: Advisor/Consultant|Ferring Pharmaceuticals: Honoraria
The molecular mechanisms regulating cell proliferation and development during the life cycle of malaria parasites remain to be elucidated. The peculiarities of the cell cycle organization during ...Plasmodium falciparum schizogony suggest that the modalities of cell cycle control in this organism may differ from those in other eukaryotes. Indeed, existing data concerning Plasmodium cell cycle regulators such as cyclin-dependent kinases reveal structural and functional properties that are divergent from those of their homologues in other systems. The work presented here lies in the context of the exploitation of the recently available P. falciparum genome sequence toward the characterization of putative cell cycle regulators. We describe the in silico identification of three open reading frames encoding proteins with maximal homology to various members of the cyclin family and demonstrate that the corresponding polypeptides are expressed in the erythrocytic stages of the infection. We present evidence that these proteins possess cyclin activity by demonstrating either their association with histone H1 kinase activity in parasite extracts or their ability to activate PfPK5, a P. falciparum cyclin-dependent kinase homologue, in vitro. Furthermore, we show that RINGO, a protein with no sequence homology to cyclins but that is nevertheless a strong activator of mammalian CDK1/2, is also a strong activator of PfPK5 in vitro. This raises the possibility that “cryptic” cell cycle regulators may be found among the 50% of the open reading frames in the P. falciparum genome that display no homology to any known proteins.
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