Research Spotlight

Defayette, A., A. Perrello, T. Brewer, J. Picano and S. Ahmed (2020). “Enteral baclofen withdrawal managed with intravenous dexmedetomidine: A case report.” Am J Health Syst Pharm Jan 13. [Epub ahead of print].

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PURPOSE: Acute enteral baclofen withdrawal can be clinically severe if not identified and managed appropriately. Treatment of baclofen withdrawal includes supportive care and reinitiation of baclofen. There are limited pharmacotherapeutic interventions available to manage symptoms of acute enteral baclofen withdrawal, especially in nonintubated patients. SUMMARY: We describe a 61-year-old Caucasian male with a past medical history of chronic back pain and spinal stenosis who was admitted to the medical intensive care unit with confusion, insomnia, agitation, delirium, and auditory and visual hallucinations. For control of agitation, the patient was administered 10 mg of i.v. haloperidol, 1 mg of i.v. lorazepam, and 14 mg of i.v. midazolam, with minimal improvement noted; therefore, dexmedetomidine was initiated, which led to clinical resolution of his symptoms. Upon further investigation it was determined that the patient was taking approximately 10 baclofen 20-mg tablets a day. According to his pharmacy records, he had filled prescriptions for a total of 738 baclofen tablets in the previous 12 weeks. The patient’s presentation and sudden discontinuation of high-dose baclofen led to a diagnosis of baclofen withdrawal. Baclofen was subsequently restarted, and dexmedetomidine was weaned over 36 hours. CONCLUSION: Dexmedetomidine controlled this patient’s agitation and delirium without suppressing his respiratory drive and should be considered for management of acute enteral baclofen withdrawal.

Xenogiannis, I., D. Karmpaliotis, K. Alaswad, F. A. Jaffer, R. W. Yeh, M. Patel, E. Mahmud, J. W. Choi, M. N. Burke, A. H. Doing, P. Dattilo, C. Toma, B. Uretsky, O. Krestyaninov, D. Khelimskii, E. Holper, S. Potluri, R. M. Wyman, D. E. Kandzari, S. Garcia, M. Koutouzis, I. Tsiafoutis, J. J. Khatri, W. Jaber, H. Samady, B. K. Jefferson, T. Patel, J. W. Moses, N. J. Lembo, M. Parikh, A. J. Kirtane, Z. A. Ali, F. Gkargkoulas, P. Tajti, A. B. Hall, B. V. Rangan, S. Abdullah, S. Banerjee and E. S. Brilakis (2020). “Impact of concomitant treatment of non-chronic total occlusion lesions at the time of chronic total occlusion intervention.” Int J Cardiol 299: 75-80.

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BACKGROUND: During chronic total occlusion (CTO) percutaneous coronary intervention (PCI), sometimes non-CTO lesions are also treated. METHODS: We compared the clinical and procedural characteristics and outcomes of CTO PCIs with and without concomitant treatment of a non-CTO lesion in a contemporary multicenter CTO registry. RESULTS: Of the 3598 CTO PCIs performed at 21 centers between 2012 and 2018, 814 (23%) also included PCI of at least one non-CTO lesion. Patients in whom non-CTO lesions were treated were older (65+/-10 vs. 64+/-10years, p=0.03), more likely to present with an acute coronary syndrome (32% vs. 23%, p<0.01), and less likely to undergo PCI of a right coronary artery (RCA) CTO (46% vs. 58%, p<0.01). The most common non-CTO lesion location was the left anterior descending artery (31%), followed by the circumflex (29%) and the RCA (25%).Combined non-CTO and CTO-PCI procedures had similar technical (88% vs. 87%, p=0.33) and procedural (85% vs. 85%, p=0.74) success and major in-hospital complication rates (3.4% vs. 2.7%, p=0.23), but had longer procedure duration (131 [88, 201] vs. 117 [75, 179] minutes, p<0.01), higher patient air kerma radiation dose (3.0 [1.9, 4.8] vs. 2.8 [1.5, 4.6] Gray, p<0.01) and larger contrast volume (300 [220, 380] vs. 250 [180, 350] ml, p<0.01). CONCLUSIONS: Combined CTO PCI with PCI of non-CTO lesions is associated with similar success and major in-hospital complication rates compared with cases in which only CTOs were treated, but requires longer procedure duration and higher radiation dose and contrast volume.

Wong, F., E. Bendel, K. Sniderman, T. Frederick, Z. J. Haskal, A. Sanyal, S. K. Asrani, J. Capel and P. S. Kamath (2020). “Improvement in Quality of Life and Decrease in Large Volume Paracentesis Requirements With the Automated Low Flow Ascites Pump.” Liver Transpl Jan 30. [Epub ahead of print].

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BACKGROUND & AIMS: The alfapump is an implantable device that drains ascites directly into the urinary bladder. We studied in North American patients with cirrhosis and refractory ascites ineligible for TIPS, the safety and efficacy of the alfapump in the management of ascites. The former was assessed by absence of serious complications; and the latter by its impact on ascites control as assessed by decreased large volume paracentesis (LVP) requirement and on improvement in quality of life (QOL) as measured by chronic liver disease (CLDQ) and ascites questionnaires (Ascites Q). METHODS: Following alfapump implantation, patients were monitored for ascites control, laboratory abnormalities, QOL, adverse events and survival at 12 months (M). RESULTS: 30 patients (60.0+/-9.9 years, 57% male, MELD 11.4+/-2.7) received an alfapump mostly by an interventional radiology approach (97%), followed by long-term prophylactic antibiotics. The alfapump removed a mean ascites volume of 230.6+/-148.9L/patient at 12M, dramatically reducing the mean LVP frequency from 2.4+/-1.4 pre- to 0.22+/-0.39/patient/M post-pump implantation. 14 patients required 18 re-interventions related to pump or catheter dysfunction. All surviving patients had improved QOL (CLDQ: 3.88+/-1.21 vs. 4.98+/-1.00; Ascites Q: 51.7+/-21.9 vs. 26.7+/-18.6, baseline vs 3M, p<0.001 for both) and better biochemical index of nutritional status (prealbumin 87.8+/-37.5mg/L vs. 102.9+/-45.3mg/L at 3M, p=0.041). Bacterial infections (15 events in 13/30 patients), electrolyte abnormalities (11 events in 6/30 patients), and renal complications (11 events in 9/30 patients) were the most common severe adverse events. Four patients died by 12M of cirrhosis complications. CONCLUSION: Alfapump insertion may be a definitive treatment for refractory ascites in cirrhosis, especially in patients who are not TIPS candidates. www.clinicaltrials.gov, #NCT02400164.

Wesson, D. E., J. M. Buysse and D. A. Bushinsky (2020). “Mechanisms of Metabolic Acidosis-Induced Kidney Injury in Chronic Kidney Disease.” J Am Soc Nephrol Jan 27. [Epub ahead of print].

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Retrospective analyses and single-center prospective studies identify chronic metabolic acidosis as an independent and modifiable risk factor for progression of CKD. In patients with CKD, untreated chronic metabolic acidosis often leads to an accelerated reduction in GFR. Mechanisms responsible for this reduction include adaptive responses that increase acid excretion but lead to a decline in kidney function. Metabolic acidosis in CKD stimulates production of intrakidney paracrine hormones including angiotensin II, aldosterone, and endothelin-1 (ET-1) that mediate the immediate benefit of increased kidney acid excretion, but their chronic upregulation promotes inflammation and fibrosis. Chronic metabolic acidosis also stimulates ammoniagenesis that increases acid excretion but also leads to ammonia-induced complement activation and deposition of C3 and C5b-9 that can cause tubule-interstitial damage, further worsening disease progression. These effects, along with acid accumulation in kidney tissue, combine to accelerate progression of kidney disease. Treatment of chronic metabolic acidosis attenuates these adaptive responses; reduces levels of angiotensin II, aldosterone, and ET-1; reduces ammoniagenesis; and diminishes inflammation and fibrosis that may lead to slowing of CKD progression.

Wesson, D. E. (2020). “Serum bicarbonate as a cardiovascular risk factor: evolving from ‘non-traditional’?” Nephrol Dial Transplant Jan 31. [Epub ahead of print].

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Cardiovascular disease (CVD) remains the leading cause of premature death globally, and identifying modifiable CVD risk factors continue to be an important goal. Individuals with chronic kidney disease (CKD) suffer premature death more so than those without CKD, and do so more commonly than developing end-stage kidney disease. This enhanced CKD-related mortality is due predominantly to increased risk for, and earlier onset of, CVD including ischemic heart disease and cerebrovascular accident or stroke, the two top global CVD contributors to premature mortality. Consequently, CKD is an attractive model to study in order to identify CVD risk contributors that might be present disproportionately, but not exclusively, in CKD patients that when addressed might reduce the risk for subsequent CVD. Metabolic acidosis, reflected by reduced serum bicarbonate ([HCO3]) concentration, further increases CVD and overall mortality risk in nontransplant CKD and increases the risk for mortality and ischemic CVD events in kidney transplant recipients . . . Deciphering mechanisms as to how an acid milieu reflected by reduced serum [HCO3] appears to increase CVD risk in individuals with and without CKD will help design interventions to reduce CVD outcomes, with their devastating consequences. The report by Dobre et al. adds to the growing body of evidence that should encourage continued basic studies to determine contributing mechanisms and encourage interventional studies to determine if reducing this milieu is an effective adjunct to traditional CVD risk reduction strategies. Interventions to ameliorate this acid milieu include low acid/high base-producing diets (high in base-producing foods like fruits and vegetables and low in acid-producing food components like animal-sourced foods) and/or oral alkalies like sodium bicarbonate and sodium citrate to neutralize the accumulated acid. Such studies will also help determine if low serum [HCO3] can be moved from ‘non-traditional’ to ‘traditional’ CVD risk factors. (Excerpts from text, p. 1, 3; no abstract available; refers to Dobre M, Pajewski NM, Beddhu S et al. Serum bicarbonate and cardiovascular events in hypertensive adults: results from the Systolic Blood Pressure Intervention Trial. Nephrol Dial Transplant 2019; https://doi.org/10.1093/ndt/gfz149.)