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Introduction: Hypertensive disorders during pregnancy elevate the likelihood of unfavorable outcomes for both mother and fetus. In cases of acute hypertension, several pharmacological interventions are available to lower blood pressure, such as hydralazine, a direct arteriolar vasodilator, and labetalol, a combined alpha and beta-blocker., Objectives: This systematic review and meta-analysis of randomized controlled trials (RCTs) aims to compare the efficacy and safety of intravenous labetalol and intravenous hydralazine for acute hypertensive disorders during pregnancy., Methods: We systematically searched PubMed, Embase and Cochrane for studies comparing labetalol versus hydralazine in pregnant patients. The primary outcomes were median arterial blood pressure (MABP), diastolic blood pressure (DBP) and systolic blood pressure (SBP). We performed statistical analyses using R 4.1.1. Heterogeneity was examined with the Cochran Q test and I 2 statistics. Risk ratios (RR) and mean differences (MD) with 95% confidence intervals (CI), were computed with a random-effects model., Results: Nineteen RCTs were included in this meta-analysis, comprising 2,261 patients. Among them, 1,131 (50 %) received treatment with labetalol. There was no statistically significant difference between groups in terms of SBP (MD -1.74; 95 % CI -6.72 to 3.23; p = 0.49; I 2  = 93 %), MABP (MD -0.72; 95 % CI -2.34 to 0.90; p = 0.39; I 2  = 0 %), DBP (MD 0.25; 95 % CI -4.72 to 5.21; p = 0.92; I 2  = 96 %), tachycardia (RR 0.42; 95 % CI 0.15 to 1.18; p = 0.099; I 2  = 41 %), and placenta abruption (RR 0.42; 95 % CI 0.15 to 1.16; p = 0.093; I 2  = 0 %). However, labetalol significantly reduced maternal hypotension (RR 0.26; 95 % CI 0.21 to 0.33; p < 0.001; I 2  = 41 %) compared with hydralazine., Conclusion: This systematic review and meta-analysis of RCTs found that labetalol and hydralazine were efficient for hypertension disorders in pregnancy. However, labetalol reduced the incidence of maternal hypotension., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Context: IgM-dominant immune complex-mediated glomerulonephritis (IgM-dominant ICMGN) is a rare renal entity, characterized by a membranoproliferative pattern by light microscopy, dominant IgM staining by immunofluorescent staining, and subendothelial deposits by electron microscopy. This study was to investigate if some of IgM-ICMGN were associated with autoimmune disorders induced by hydralazine., Design: Seven IgM-dominant ICMGN cases were identified over 8 years. Their pathologic phenotypes and clinical scenarios were analyzed in detail., Results: Patients' ages ranged from 47 to 87 years old with 5 women and two men. Six of seven patients had drug-induced autoimmune phenomenon (hydralazine-induced positive ANCA and ANA). All of them had renal dysfunction and some proteinuria. Most pathologic features showed a membranoproliferative pattern of glomerulonephritis with dominant IgM deposits at subendothelial spaces. IgM nephropathy (a variant of focal segmental glomerulosclerosis), chronic thrombotic microangiopathy, and cryoglobulinemic glomerulopathy were ruled out in the cases., Conclusion: The hydralazine-induced autoimmune phenomenon can be seen in IgM-dominant ICMGN, which should be classified as a subtype of membranoproliferative glomerulonephritis.

We aimed to evaluate physiologic treatment of severe hypertension. This was a retrospective cohort study of pregnant and postpartum patients with severe hypertension (systolic blood pressure [BP] 160 mm Hg or higher or diastolic BP 110 mm Hg or higher) treated with intravenous labetalol or hydralazine at a single tertiary care center between 2013 and 2018. Patients were classified as having physiologic treatment if they had hyperdynamic physiology (pulse pressure 65 mm Hg or higher) and received labetalol or had vasoconstrictive physiology (diastolic BP 100 mm Hg or higher) and received hydralazine. The primary outcome was number of antihypertensive doses to achieve nonsevere BP. Of 1,120 patients included in the analysis, 653 had physiologic treatment and 467 had nonphysiologic treatment, with 16 (1.4%) excluded for inability to classify physiology. Physiologic treatment was associated with fewer antihypertensive doses (1.4±0.9 doses vs 1.6±1.4 doses; adjusted β -0.28, 95% CI, -0.42 to -0.14) and lower odds of medication conversion (2.5% vs 4.7%; adjusted odds ratio 0.48, 95% CI, 0.24-0.93) but no difference in time to nonsevere BP (31 minutes [interquartile range 16-66 minutes] vs 34 minutes [interquartile range 15-76 minutes]; adjusted hazard ratio 1.0, 95% CI, 0.9-1.2). Physiologic treatment of severe hypertension warrants further evaluation., Competing Interests: Financial Disclosure Akila Subramaniam disclosed that money was paid to her institution from the NIH and Novocuff. The other authors did not report any potential conflicts of interest., (Copyright © 2023 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Drug-induced vasculitis can rarely cause inflammation and necrosis of blood vessel walls of both kidney and lung tissue. Diagnosis is challenging because of the lack of difference between systemic and drug-induced vasculitis in clinical presentation, immunological workup and pathological findings. Tissue biopsy guides diagnosis and treatment. Pathological findings must be correlated with clinical information to arrive at a presumed diagnosis of drug-induced vasculitis. We present a patient with hydralazine-induced antineutrophil cytoplasmic antibodies-positive vasculitis with a pulmonary-renal syndrome manifesting as pauci-immune glomerulonephritis and alveolar haemorrhage., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Asymptomatic severe hypertension (also known as hypertensive urgency) is frequently encountered in the hospital. Previous evidence suggests that management with one-time doses of intravenous (IV) antihypertensives may increase adverse events. Despite this, single-dose treatment remains common in the emergency department and inpatient settings., Methods: This quality initiative was launched at New York City Health + Hospitals, the largest safety net hospital system in the United States. The initiative involved two changes to electronic orders for IV hydralazine and IV labetalol: a nonintrusive advisory statement within the order instructions and a mandatory requirement to document the indication for IV antihypertensive use., Results: This initiative took place from November 2021 to October 2022. Of the indications selected for IV antihypertensive orders, 60.7% were for hypertensive emergency, 15.3% were for patients who were strictly NPO, 21.2% were for other, and 2.8% selected more than one indication. For ED-only encounters, aggregate IV hydralazine and IV labetalol orders per 1,000 patient encounters were 2.53 preintervention and 1.55 postintervention (38.7% reduction, p < 0.001). For inpatient encounters, aggregate IV hydralazine and IV labetalol orders per 1,000 patient-days were 18.25 preintervention and 15.81 postintervention (13.4% reduction, p < 0.001). Similar trends were observed for individual orders of IV hydralazine and IV labetalol. There were significant reductions in 7 of the 11 hospitals in inpatient administration of aggregate IV hydralazine and labetalol orders per 1,000 patient-days., Conclusion: This quality improvement initiative successfully reduced unnecessary IV antihypertensive use in an 11-hospital safety net system., (Copyright © 2023 The Joint Commission. Published by Elsevier Inc. All rights reserved.)

Purpose: Hydralazine, doxazosin, and verapamil are currently recommended by the Endocrine Society as acceptable bridging treatment in those in whom full cessation of antihypertensive medication is infeasible during screening for primary aldosteronism (PA). This is under the assumption that they cause minimal to no effect on the aldosterone-to-renin ratio, the most widely used screening test for PA. However, limited evidence is available regarding the effects of these particular drugs on said ratio., Methods: In the present study, we retrospectively assessed the changes in aldosterone, renin, and aldosterone-to-renin values in essential hypertensive participants before and after treatment with either hydralazine (n = 26) or doxazosin (n = 20) or verapamil (n = 15). All samples were taken under highly standardized conditions., Results: Hydralazine resulted in a borderline significant rise in active plasma renin concentration (19 vs 25 mIU/L, p = 0.067) and a significant fall in the aldosterone-to-renin ratio (38 vs 24, p = 0.017). Doxazosin caused declines in both plasma aldosterone concentration (470 vs 330 pmol/L, p = 0.028) and the aldosterone-to-renin ratio (30 vs 20, p = 0.020). With respect to verapamil, we found no statistically significant effect on any of these outcome variables., Conclusion: We conclude that the assumption that these drugs can be used with little consequence to the aldosterone-to-renin cannot be substantiated. While it is possible that they are indeed the best option when full antihypertensive drug cessation is infeasible, the potential effects of these drugs must still be taken into account when interpreting the aldosterone-to-renin ratio., (© 2021. The Author(s).)

Objectives: To compare the efficacy of intravenous Labetalol and intravenous Hydralazine in reduction of blood pressure in patients with severe pre-eclampsia., Methodology: This comparative study was conducted at the Department of Obstetrics and Gynecology at Ziauddin University Hospital, Karachi from1st June 2019 to 30th June 2020. Total 208 pregnant women having severe pre-eclampsia (systolic pressure ≥160 mmHg and diastolic pressure ≥110mmHg) were included in study. Group A received I/V Labetalol. Group B received I/V Hydralazine. Efficacy of drugs was observed by reduction in blood pressure and the number of doses administered. Data was analysed using SPSS version 26., Results: Systolic blood pressure reduction in Labetalol group was significantly lower than in hydralazine group (105.5 ±11.3 vs. 115.8 ±17.1, p≤ 0.001). Diastolic blood pressure reduction was also lower in labetalol group than in hydralazine group (p= 0.03). Number of dosage of drugs in Group A (Labetalol) was 3.2 ±1.2 vs. Group B (Hydralazine) was 4.4±1.4, p =0.006)., Conclusion: The results of this study show that Labetalol is more effective as compared to Hydralazine in terms of reducing the systolic and diastolic blood pressure and number of doses (Drugs) for in patients with severe preeclampsia., Competing Interests: none, (© 2023 Kausar M et al.)

Drug-induced liver injury resulting in fulminant liver failure is a well-known condition, and many drugs have been documented in the literature as possible etiologies. However, hydralazine has seldom been reported as the offending agent. Our case report is about one such rare scenario of fulminant liver failure due to hydralazine use as an antihypertensive. A 65-year-old female patient presented with signs of fulminant liver failure 2 months after starting hydralazine for hypertension. She underwent extensive workup for the cause of acute liver failure. Other possible medications were ruled out, and workup for autoimmune and other etiologies were also negative. The patient underwent a deceased donor liver transplant and has been doing well since then. Her liver was found to be atrophic, with microscopically confirmed drug-induced liver injury. Hydralazine is used orally to treat essential hypertension and intravenously to emergently lower blood pressure. Hydralazineinduced acute liver failure is extremely rare. However, in this rare case where hydralazine-related drug-induced liver injury worsened to the extent of requiring liver transplant, we felt obliged to document and highlight this complication as a form of reminder to our colleagues of this serious outcome.

Background: Miscarriage is the most frequent cause of pregnancy loss, affecting 15-20% of clinically recognized pregnancies. Early uterine vascular insufficiency (EUVI), defined as abnormal uterine artery (UA) Doppler impedance indices in early pregnancy, is present in two-thirds of pregnancies ending in miscarriage after embryonic cardiac activity has been detected. There is currently no available therapy for reducing the risk of miscarriage in these cases., Objective: To determine whether vasodilator therapy with hydralazine can reduce abnormally high UA impedance indices and miscarriage rates in pregnancies with EUVI when administered from before 9 weeks' gestation until completing 13 weeks' gestation., Methods: A total of 253 consecutive singleton pregnancies with a live embryo and scanned before 9 weeks' gestation were included in the study. Ninety-two pregnancies (36.3%) were classified as having EUVI. Hydralazine was administered in daily doses of 50 mg, starting 24-36 h after the initial diagnosis of EUVI and continuing throughout the first trimester. The miscarriage rate in the hydralazine-treated EUVI group was compared with the one observed in our previously reported untreated cohort and the pregnancies with EUVI that declined treatment with hydralazine., Results: The miscarriage rate among the hydralazine-treated EUVI group was significantly lower than the previously reported untreated cohort (7.8% versus 26.2%, p  = .003; odds ratio (OR) = 4.3, 95% confidence interval (CI) = 1.6-11.9). In 15 untreated pregnancies with EUVI, the miscarriage rate was similar to that of the previously reported untreated cohort (26.7% versus 26.2%; p  = .603) and higher than the hydralazine-treated group (26.7% versus 7.8%, p  = .05; OR = 4.4, 95% CI = 1.1-18.2)., Conclusions: Hydralazine therapy in pregnancies with EUVI was associated with a significant decrease in the rate of miscarriage. We suggest a sequence of events leading to a higher risk of miscarriage in pregnancies with EUVI and propose a potential mechanism through which hydralazine may reduce this risk.

Competing Interests: The authors have no conflicts of interest to declare.

Objectives: The objectives were to compare the efficacy and safety of intravenous hydralazine and labetalol for acutely lowering severe hypertension in pregnancy., Study Design: This was a superiority parallel double-blinded randomized controlled trial conducted from October 2018 to June 2019 in two hospitals in Gombe, Nigeria. Pregnant women with a live singleton fetus at gestational age of at least 28 weeks with severe hypertension were randomized (60 per group) to receive incremental doses of either intravenous labetalol (20 mg; 40 mg; 80 mg; 80 mg; and 80 mg) or 10 mg of intravenous hydralazine - up to a maximum of 5 doses - until the target blood pressure was achieved or the study was terminated., Main Outcome Measures: The main outcome measures were the mean reduction in mean arterial blood pressure and occurrence of persistent hypertension. Other endpoints were maternal side-effects, perinatal death, Apgar score at birth and SCBU admission., Results: One hundred and thirteen patients' data were analyzed (fifty-six [56] in the hydralazine group and fifty-seven [57] in the labetalol group). There were no significant differences in the fall of the mean arterial blood pressure (labetalol; 24.19 mmHg/hydralazine; 27.68 mmHg) (p = 0.192), maternal side effects, perinatal deaths, Apgar scores and SCBU admission between the two groups. Hydralazine, however, produced a more marked reduction in diastolic blood pressure than labetalol (p = 0.012)., Conclusion: Both labetalol and hydralazine are effective for acute blood pressure control in pregnancy with a similar safety profile. This study was self-funded and registered in the Pan African Clinical Trials Registry (www.pactr.orgPACTR202010738538062)., (Copyright © 2022 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.)

Hydralazine is a commonly prescribed antihypertensive agent. Some of its labelled adverse reactions include lupus-like syndrome, tachycardia, headache and fever. Despite its well-known side effects, little is known about hydralazine's hepatotoxic effects. We report the case of a 54-year-old female patient who was started on hydralazine for hypertension management but later presented with hydralazine-induced liver injury. Her initial presentation consisted of non-specific symptoms and a hepatocellular injury pattern. Liver biopsy revealed hepatic steatosis. Three weeks after discontinuation of hydralazine, the patient's liver enzymes normalised, and her symptoms resolved. Few studies have examined the incidence and mechanism by which hydralazine induces a liver injury pattern. With this case, we review the literature, the pathogenesis involved and the eventual management of hydralazine-induced liver injury. We propose close monitoring of liver enzymes for patients on hydralazine throughout their treatment course., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Hydralazine, a widely used therapy for hypertension and heart failure, can elicit autoimmune disease, including anti-neutrophil cytoplasmic antibody associated glomerulonephritis (ANCA-GN). We identified 80 cases of ANCA-GN complicating treatment with hydralazine, accounting for 4.3% (80/1858 biopsies) of ANCA-GN diagnosed between 2006 and 2019. Over three-fourths of patients were on hydralazine for at least one year, with mean daily dose of approximately 250 mg/day. ANCA testing revealed p-ANCA/myeloperoxidase-ANCA seropositivity in 98%, including 39% with dual p-ANCA/myeloperoxidase-ANCA and cANCA/anti-protinase 3-ANCA positivity, often accompanied by anti-nuclear antibody (89%), anti-histone antibody (98%), and hypocomplementemia (58%). Kidney biopsy revealed necrotizing and crescentic glomerulonephritis, similar to primary ANCA-GN, but significantly less frequently pauci-immune (77 vs. 100%) and more commonly associated with mesangial hypercellularity (30 vs. 5%), electron dense deposits (62 vs. 20%), and endothelial tubuloreticular inclusions (11 vs. 0%); all significant differences. On follow-up, 42 of 51 patients received induction immunosuppression: 19 reached the combined end-points of kidney failure or death and 32 had mean creatinine of 1.49 mg/dL at last follow-up. Thus, hydralazine-associated ANCA-GN often exhibits overlapping clinical and pathologic features of mild immune complex glomerulonephritis resembling lupus nephritis. With discontinuation of hydralazine and immunosuppression, outcomes are similar to primary ANCA-GN., (Copyright © 2021 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Background: Current guidelines for the management of asymptomatic hypertension (HTN) in the inpatient setting recommend the use of oral antihypertensives. However, in clinical practice, intravenous (IV) antihypertensives are commonly utilised with little supporting evidence. The objective of this study was to evaluate literature examining the safety/efficacy of IV hydralazine and labetalol in hospitalised patients with non-emergent, asymptomatic HTN., Methods: The PRISMA guidelines were utilised to structure the systematic review. A search strategy composed of drug-, inpatient- and HTN-related terms was conducted utilising PubMed, Embase and Scopus databases through May 2020. Full-text, English-language articles describing IV labetalol and/or hydralazine use for non-emergent HTN in an inpatient setting that focused on clinical outcomes (ie vitals, adverse effects, healthcare utilisation) were included. Identified studies were screened/extracted using DistillerSR by two reviewers at each stage, and studies were evaluated qualitatively for the presence of bias., Results: From 3362 records identified in the search, a final set of 10 articles were identified. Four studies focused on labetalol (40%), five studies on hydralazine and labetalol (50%), and one study on hydralazine (10%). The included studies presented a variety of outcomes, but several trends were identified, including reduction in average blood pressure in eight (80%) studies, a risk of adverse effects in six (60%) and increased length of stay in one (10%)., Discussion: The studies identified in this review raise concerns regarding the safety of IV hydralazine and labetalol in non-emergent HTN. Despite relatively broad clinical experience with these drugs, experimental investigations regarding their utility are recommended., (© 2021 John Wiley & Sons Ltd.)

BACKGROUND Hydralazine, a potent vasodilator widely used to treat hypertension, has been implicated in an increasing number of cases of drug-induced autoimmune diseases in recent years. However, antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis secondary to hydralazine use has rarely been described and most reported cases involved multi-organ-related vasculitis, including skin and lung-kidney manifestations. ANCA-associated vasculitis is an immune-inflammatory condition characterized by necrotizing vasculitis with few or no immune deposits, predominantly affecting small vessels. The fact that the vasculitis is associated with hydralazine use and improves with discontinuation of hydralazine supports the diagnosis of hydralazine-induced disease. The case we report is a hydralazine-induced, ANCA-associated, pauci-immune crescentic glomerulonephritis with a presentation limited to the kidneys. CASE REPORT A 66-year-old woman was admitted to the hospital for worsening renal function over a month with no symptoms. Serology work-up was significantly positive for antinuclear, perinuclear ANCA, anti-histone, anti-double-stranded DNA, anti-cardiolipin, and anti-myeloperoxidase antibodies. The patient ultimately underwent a kidney biopsy, which revealed pauci-immune crescentic glomerulonephritis. Her kidney function improved with cessation of hydralazine as well as therapy with pulse steroids. CONCLUSIONS Hydralazine is commonly prescribed to treat hypertension. Healthcare providers should be aware of potentially severe hydralazine-induced ANCA-associated vasculitis, which can present with various clinical manifestations. Serologic studies have indicated that it has features that overlap with lupus. Biopsy is helpful for making a definitive diagnosis and developing individual treatment plans. Early diagnosis, cessation of the offending drug, and initiation of immunosuppressive therapy are key for favorable prognosis.

Hydralazine is a common arterial vasodilator used in the management of congestive heart failure and hypertension. It can be associated with drug-induced lupus and less commonly antineutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV). Drug-induced AAV typically has a favourable long-term prognosis. It is not commonly associated with primary skin involvement, as most cases also have notable kidney and lung disease. Cases with isolated skin findings are rare. We present a rare case of a 60-year-old woman on long-term hydralazine who presented with AAV with primary skin and mucosal involvement, in the form of diffuse bullous and ulcerative lesions, which posed a diagnostic challenge. Her hospital course was marked by several complications including disseminated intravascular coagulation. She required intensive therapy with high-dose steroids, plasmapheresis and rituximab. She tolerated immunosuppression well and with multidisciplinary supportive care, she recovered well and was able to be discharged from the hospital., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Hydralazine, an arterial vasodilator, is a widely used medication for the management of hypertension and heart failure, especially for patients who cannot tolerate the use of ACEIs or ARBs. It is generally well-tolerated and has a safe profile in pregnancy. However, hydralazine can induce immune-mediated side effects, such as hydralazine-induced lupus and less commonly hydralazine- induced ANCA vasculitis. The latter most commonly affects the kidneys with or without other organ involvement. There are several cases reported in the literature of hydralazine-induced ANCA associated vasculitis (AAV) that have pulmonary manifestations, also known as hydralazine- induced pulmonary-renal syndrome (PRS), a condition with a high risk of mortality. We are reporting a case of Hydralazine-induced ANCA associated glomerulonephritis with severe diffuse alveolar hemorrhage (DAH). In addition, we will review the current literature and discuss the importance of prompt diagnosis and early management to decrease mortality and morbidity associated with this serious condition., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Response to acute treatment of severe hypertension during pregnancy in Asian women was not known. Labor and delivery checklists of Thai women treated with intravenous hydralazine or labetalol for systolic blood pressure (SBP) ≥ 160 or diastolic blood pressure (DBP) ≥ 110 mm Hg from January 2011 to December 2013 were reviewed as parts of an audit. Primary outcome was prompt achievement of SBP 140-150 and DBP 90-100 mm Hg after the first bolus. Secondary outcomes were medication-related undesired effects. The mean ± standard deviation age and prevalence of chronic hypertension in hydralazine (n = 62) versus labetalol (n = 64) groups were 32.5 ± 6 versus 29.9 ± 6.8 years and 50% versus 21.9%, respectively (P < .05). Magnesium sulfate was promptly administered on admission to every woman to prevent seizure. Targeted blood pressure was timely achieved in 41.9% and 67.2% of the hydralazine and labetalol groups, respectively (P < .05). Nonreassuring fetal heart rate occurred in 51.6% and 32.8% of the hydralazine and labetalol groups, respectively (P = .05). The prevalence of cesarean section and Apgar score < 7 were not significantly different (P > .05). Real-life clinical experiences suggested significant advantages of intravenous labetalol over hydralazine in pregnant women with severe hypertension., (© 2020, The American College of Clinical Pharmacology.)

Background: Combination therapy with isosorbide dinitrate (ISD) and hydralazine (HY) reduces heart failure mortality. The safety and tolerability in individuals requiring maintenance hemodialysis (HD) is unknown., Methods: Single-center, randomized, placebo-controlled, double-blind pilot trial to explore safety and tolerability of ISD/HY in maintenance HD. Participants were randomized to placebo or combination ISD/HY. Dose was escalated over 3 weeks from ISD 10 mg/HY 10 mg to ISD 40 mg/HY 75 mg three times per day with the maximum tolerated dose maintained for the subsequent 21 weeks. Primary endpoints included adverse events, adverse events precluding further treatment with study medication, serious hypotension ( i.e ., requiring hospitalization or emergency room visit), and recurrent intra-dialytic hypotension. Efficacy signals included change in mitral annular E' velocity by tissue Doppler echocardiography and change in left ventricular coronary flow reserve on positron emission tomography., Results: A total of 17 individuals were randomized to ISD/HY ( N =7) or placebo ( N =10). All participants assigned to ISD/HY completed dose escalation to 40/75 mg, but dose reductions were required in two participants. No participants discontinued therapy. There were no serious hypotension events. Recurrent intradialytic hypotension was less frequent with ISD/HY (0.47 events/patient-year) than placebo (1.83 events/patient-year, P =0.04). In contrast, nausea (ISD/HY, 1.90 events/patient-year; placebo, 0.50 events/patient-year, P =0.03) was significantly more frequent, and headache and diarrhea were numerically but not significantly more frequent with ISD/HY. Adverse events were more frequent with ISD/HY (11.4 events/patient-year) than placebo (6.31 events/patient-year). We did not detect between-group differences in the change in E' ( P =0.34); ISD/HY showed a mean increase of 0.6 cm/s (SD 1.1), and placebo showed a mean decrease of 0.04 cm/s (SD 0.9). Changes in coronary flow reserve were minimal, -0.3 (0.2) with ISD/HY and -0.03 (0.5) in the placebo group, P =0.19., Conclusions: ISD/HY appears to be well tolerated in patients being treated with maintenance HD, but headache and gastrointestinal side effects occur more frequently with ISD/HY compared with placebo., Competing Interests: D. Charytan reports receiving research support from Gilead, Janssen, Medtronic Inc, and NovoNordisk, and consulting fees or fees for service on data safety or clinical events committees from Allena Pharmaceuticals, AstraZeneca, Fresenius, Gilead, Janssen, Merck, and NovoNordisk. L. Dember reports receiving compensation from the National Kidney Foundation for serving as Deputy Editor of the American Journal of Kidney Diseases, and consulting fees from Merck. M. DiCarli reports receiving research grants from Gilead Sciences and SpectrumDynamics, and consulting honoraria from Sanofi and General Electric. T. Ikizler reports receiving personal fees from Abbott Renal Care, Fresenius Kabi, and the International Society of Nephrology during the conduct of the study. R. Mehrotra reports receiving honoraria from Baxter HealthCare and he is a member of the Board of Trustees of the Northwest Kidney Centers. H. Skali reports receiving stock options from OptimizeRx for consulting/advisory roles, outside the submitted work. S. Waikar reports receiving grants and personal fees from Allena Pharmaceuticals and personal fees from Barron and Budd (versus Fresenius), Bunch and James, Cerus, Consumer Value Store, GE Health Care, Glaxo Smith Kline, Harvard Clinical Research Institute (aka Baim), Johnson and Johnson, Kantum Pharma, Mallinckrodt, Mass Medical International, Public Health Advocacy Institute Pfizer, Roth Capital Partners, Strataca, Takeda, Venbio, and Wolters Kluewer, outside the submitted work. All remaining authors have nothing to disclose., (Copyright © 2020 by the American Society of Nephrology.)

Background: Hydralazine is a common vasodilator which has been used for the treatment of hypertension and heart failure. Hydralazine can induce antineutrophil cytoplasmic antibody-associated vasculitis due to its auto-immunogenic capability and one of the very rare presentations is pulmonary-renal syndrome., Case Presentation: We report a case of a 64-year-old African American woman, who presented to our emergency room with shortness of breath, orthopnea, paroxysmal nocturnal dyspnea, leg swelling, fatigue, loss of appetite, cough with clear sputum, and lightheadedness. On admission, she developed acute hypoxic respiratory failure requiring intubation and acute renal failure requiring hemodialysis. A serologic workup was positive for antineutrophil cytoplasmic antibody, antinuclear antibody, anti-histone, anti-cardiolipin IgM, and anti-double-stranded DNA antibodies. A renal biopsy was done due to persistent deterioration in kidney function and demonstrated classic crescentic (pauci-immune) glomerulonephritis. Hydralazine was empirically discontinued early in the admission and she was started on corticosteroids and cyclophosphamide following biopsy results. She was clinically stable but remained dependent on hemodialysis after discharge., Conclusion: Hydralazine-induced antineutrophil cytoplasmic antibody-associated vasculitis with pulmonary-renal syndrome is a rare occurrence. In the setting of hydralazine use, multiple positive antigens, and multisystem involvement, clinicians should consider this rare condition requiring prompt cessation of offending drug, early evaluation with biopsy, and contemplate empiric immunosuppressive therapy while biopsy confirmation is pending.

Despite its long history of untoward side effects of a systemic autoimmune disease, drug-induced lupus can be difficult to recognize because of the disconnect between chronic drug usage and onset of symptoms. In this case, the patient was treated with hydralazine for two years when symptoms were initially reported, but a diagnosis of hydralazine-induced lupus was not considered for another half year. Despite treatment with steroidal and nonsteroidal anti-inflammatory medications during this period, rheumatologic symptoms and signs continued to deteriorate, consistent with the diagnosis of systemic lupus erythematosus. Not until the patient voluntarily discontinued hydralazine did symptoms begin to improve, fully resolving over the subsequent 6-12 months largely in the absence of anti-inflammatory medication. This patient demonstrates that failure to recognize a drug-induced disease etiology can result in substantial worsening of rheumatologic symptoms over the subsequent six months, ultimately satisfying criteria for systemic lupus erythematosus. While symptoms and signs largely normalized, some laboratory abnormalities and occasional arthralgia remained two years after discontinuing hydralazine, suggesting smoldering inflammatory disease.

Intravenous (IV) hydralazine, enalapril and labetalol are oftentimes used without indication for the treatment of asymptomatic hypertension in the hospital setting and have been shown to have substantial adverse effects that are associated with increased morbidity and mortality, as well as longer length of stay. Their use is also associated with greater monetary costs. In this project, we studied the frequency of use and consequences of these medications before and after a series of education cycles which clarified when and when not to use intravenous antihypertensives (IVAHs). Our initial aim was to decrease the unindicated use of IVAH by at least 25% in the setting of asymptomatic hypertension in our community hospital within a 1-year period after introducing education on the topic. Multidisciplinary involvement throughout three Plan-Do-Study-Act (PDSA) cycles yielded favourable results. We focused on education towards a hospital-wide knowledge gap stemming from a lack of guidelines regarding the treatment of asymptomatic hypertension, as well as the guideline indications for IVAH. After three cycles of education targeting different groups, the unindicated use of IVAH fell by a total of 66%, decreasing patient exposure by approximately 248 cases over the total course of the study and ultimately, yielding a 52% increase in patient safety. Secondary outcome included a reduction in cost. It was noted that IV drugs cost more than their oral counterparts. The culture change in switching away from IVAH unless otherwise indicated was driven by repetitive education and group discussion to close the gap created by a lack of guidelines., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To report the successful treatment of postoperative posterior ischemic optic neuropathy (PION) with hyperbaric oxygen therapy and to review the current literature on the pathogenesis and treatment of PION., Observations: During an angiographic procedure at a community hospital, an elderly woman had a transient drop in blood pressure after receiving an intravenous dose of hydralazine. During recovery, the patient experienced bilateral vision loss. She was transferred to our specialty referral center for treatment with hyperbaric oxygen. We followed Table 5 in the U.S. Navy Diving Manual, the protocol for decompression sickness. Our patient's vision improved markedly immediately after the first session and continued to improve throughout the course of treatment to its completion. Follow-up ophthalmology visits found the patient's vision to be close to baseline., Conclusions and Importance: PION is a rare condition. It has been difficult to determine a successful therapeutic approach because of the lack of large case-controlled studies. Hyperbaric oxygen has been used to treat other ischemic ophthalmic conditions, but there are only few reports of its use in patients with PION. Systemic steroids and antiplatelet therapy have also been used, with mixed success. In our patient, the combination of hyperbaric oxygen therapy and steroids was successful in restoring vision after postoperative PION., Competing Interests: The authors of this paper declare no conflicts of interest exist with this submission., (Copyright© Undersea and Hyperbaric Medical Society.)

Neonatal hypertension is increasingly recognized as dramatic improvements in neonatal intensive care, advancements in our understanding of neonatal physiology, and implementation of new therapies have led to improved survival of premature infants. A variety of factors appear to be important in determining blood pressure in neonates, including gestational age, birth weight, and postmenstrual age. Normative data on neonatal blood pressure values remain limited. The cause of hypertension in an affected neonate is often identified with careful diagnostic evaluation, with the most common causes being umbilical catheter-associated thrombosis, renal parenchymal disease, and chronic lung disease. Clinical expertise may need to be relied upon to decide the best approach to treatment in such patients, as data on the use of antihypertensive medications in this age group are extremely limited. Available data suggest that long-term outcomes are usually good, with resolution of hypertension in most infants. In this review, we will take a case-based approach to illustrate these concepts and to point out important evidence gaps that need to be addressed so that management of neonatal hypertension may be improved.

Objective: Drug-induced lupus (DIL) is an idiosyncratic side effect of treatments in which symptoms overlap with those of systemic lupus erythematosus (SLE). The spectrum of DIL constantly evolves with that of the pharmacopoeia. Here, we used VigiBase, the WHO global individual case safety reports (ICSRs) database, to identify the main drugs associated with DIL., Methods: We analysed all ICSRs classified as 'systemic lupus erythematosus' according to the Medical Dictionary for Drug Regulatory Activities term (preferred term level) in VigiBase. The drugs considered in the analysis were those not used to treat SLE, with a positive lower end of the 95% credibility interval for the information component (IC 025 ) ≥0, an indicator value for disproportionate Bayesian reporting., Results: A total of 12 166 DIL ICSRs were identified using VigiBase. From those, 8163 ICSRs reporting on 118 suspected drugs with IC 025 ≥0 were extracted. The median age at DIL onset was 49 years and the female to male sex ratio was 4.3. The median delay between start of suspected treatment and DIL occurrence was 172 days. DIL was reported as serious adverse event in 55.4%. Among the 118 suspected drugs, 42 had not been previously reported in association with DIL. The drugs associated with the highest number of DIL cases were infliximab, adalimumab, etanercept, procainamide and hydralazine., Conclusion: This study enables the identification of 118 drugs associated with DIL. The list of suspected drugs may prove useful to physicians when confronted with potential DIL cases., Trial Registration Number: NCT03480529., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Glucose-6-phosphate dehydrogenase (G6PD) deficiency can present a diagnostic dilemma owing to the varying degrees of disease severity and the wide range of precipitating factors. Here, we report a case of a 56-year-old man who presented with signs and symptoms of heart failure and, during the course of treatment, developed intravascular hemolysis. On investigation, he was found to be G6PD deficient. Following discontinuation of the fixed-dose combination of isosorbide dinitrate and hydralazine, the clinical condition of the patient improved, and there were no further episodes of hemolysis. The case highlights the need for a high degree of suspicion of G6PD deficiency in patients with unexplained signs and symptoms of intravascular hemolysis.

Hydralazine, a vasodilator, is commonly used as an adjunctive treatment for moderate to severe hypertension, heart failure and hypertensive emergencies in pregnancy. Hydralazine-induced lupus was first described in 1953. Clinical presentation ranges from arthralgia, myalgia, petechiae, or rash to single or multiorgan involvement. An occurrence of systemic vasculitis is a rare complication. When presented as the pulmonary-renal syndrome, it could have a rapidly progressive course which can be fatal. Here, we describe a case of hydralazine-associated rapidly progressive glomerulonephritis and pulmonary haemorrhage. We use this case to review the current literature and discuss and highlight the importance of a high degree of clinical acumen, early diagnosis and prompt treatment for better clinical outcomes., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2018. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: This study aims to characterize the development of tachycardia after intravenous hydralazine administration during Phase I recovery., Design: Retrospective observational study design., Methods: The medical records of 745 adult surgical patients who were administered hydralazine during Phase I recovery between January 1, 2010 and December 31, 2014 were electronically reviewed to characterize episodes of tachycardia., Findings: Seventy patients (94.0 cases per 1,000 administrations; 95% confidence interval = 74.0 to 117.2) developed tachycardia with a median increase of 23 beats per minute (bpm; interquartile range [IQR] = 15 to 37), a maximum rate of 106 bpm (IQR = 103 to 111; range = 101 to 131), and duration of 28 minutes (IQR = 5 to 86). The median onset of tachycardia was 43 minutes (IQR = 20 to 93), with 40% occurring after the first hour. Tachycardia was associated with female sex (P < .001), younger age (P < .001), and those with lesser comorbidities (P < .009)., Conclusions: A sizeable proportion of cases of tachycardia associated with hydralazine administration occurred after 1 hour, suggesting that these patients who may not tolerate a faster heart rate warrant longer duration of monitoring., (Copyright © 2017 American Society of PeriAnesthesia Nurses. Published by Elsevier Inc. All rights reserved.)

Introduction: Hydralazine is an antihypertensive medication that has been associated with drug-induced lupus erythematosus (DIL) as well as ANCA-associated vasculitis (AAV). Although rare, early diagnosis is critical since drug cessation is the mainstay of therapy. This retrospective study aims to characterize the clinical, laboratory, and histopathologic features of this disease., Methods: Once approval was obtained from the Institutional Review Board at the University of Iowa, all patients carrying a diagnosis of vasculitis (ICD9 code: 447.6 or ICD10 code: I77.6, I80, L95, M30, or M31) and positive ANCA lab results over the past 15 years were identified. Age, gender, comorbid conditions, medications taken over the prior 6 months, laboratory data, including electrolytes, urine studies and serologies, chest x-rays, CT scans, and pathologic biopsy records were abstracted from the electronic medical record., Results: 323 cases of AAV were identified, of which 12 were exposed to hydralazine, all at the time of diagnosis. The average duration of hydralazine therapy was 22 months and mean cumulative dose was 146g. Patients were typically older (70.3 years old) with slight female preponderance (7 females). Eleven patients presented with dyspnea, fatigue, and unintentional weight loss. Five had polyarthralgias and 8 had lower extremity petechiae. All 12 patients were both ANA and ANCA positive. ANA titers ranged from 1:160 and 1:2560. Ten were of diffuse pattern while 2 were nucleolar. ANCA titers ranged from 1:320 to 1:2560. Eleven had a pANCA pattern while one had cANCA. All 12 patients were positive for histone and 11 were positive for myeloperoxidase antibodies. Eleven also had dsDNA antibodies, and 4 had anti-cardiolipin IgG or IgM antibodies. Nine patients were also hypocomplementemic (mean C3 level: 88.4mg/dL; mean C4 level: 16.5mg/dL). All patients had variable levels of proteinuria (1+ to 3+) and eleven had active urine sediment. Urine protein:creatinine ratios ranged from 0.2 to 1.7. Of the 6 patients who underwent kidney biopsy, all 6 showed pauci-immune crescentic glomerulonephritis. Seven patients had bilateral pulmonary interstitial infiltrates and four had pleural effusions on CT scan. Four had pericardial effusions as demonstrated by echocardiography., Conclusions: Hydralazine-associated vasculitis is a drug-associated autoimmune syndrome that presents with interstitial lung disease, hypocomplementemia, and pauci-immune glomerulonephritis. Patients have elements of both DIL and DIV, as manifested by high ANA and ANCA titers as well as the presence of histone and MPO antibodies. Further research is needed to understand the etiopathogenesis of this condition., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Aims: Several antihypertensive drugs are used in the treatment of severe hypertension in pregnancy. The present study is a network meta-analysis comparing the efficacy and safety of these drugs., Methods: Electronic databases were searched for randomized clinical trials comparing drugs used in the treatment of severe hypertension in pregnancy. The number of women achieving the target blood pressure (BP) was the primary outcome. Doses required and time taken for achieving the target BP, failure rate, and incidences of maternal tachycardia, palpitation, hypotension, headache, and neonatal death and stillbirth were the secondary outcomes. Mixed treatment comparison pooled estimates were generated using a random-effects model. Odds ratios for the categorical and mean difference for the numerical outcomes were the effect estimates., Results: Fifty-one studies were included in the systematic review and 46 in the meta-analysis. No significant differences in the number of patients achieving target BP was observed between any of the drugs. Diazoxide [-15 (-20.6, -9.4)], nicardipine [-11.8 (-22.3, -1.2)], nifedipine/celastrol [-19.3 (-27.4, -11.1)], nifedipine/vitamin D [-17.1 (-25.7, -9.7)], nifedipine/resveratrol [-13.9 (-22.6, -5.2)] and glyceryl trinitrate [-33.8 (-36.7, -31)] were observed to achieve the target BP (in minutes) more rapidly than hydralazine. Nifedipine required fewer doses than hydralazine for achieving the target BP. Glyceryl trinitrate and labetalol were associated with fewer incidences of tachycardia and palpitation respectively than hydralazine. Trial sequential analysis concluded adequate evidence for hydralazine and nifedipine compared with labetalol. Moderate quality of evidence was observed for direct comparison estimate between labetalol and hydralazine but was either low or very low for other comparisons., Conclusion: The present evidence suggests similar efficacy between nifedipine, hydralazine and labetalol in the treatment of severe hypertension in pregnancy. Subtle differences may exist in their safety profile. The evidence is inadequate for other drugs., (© 2018 The British Pharmacological Society.)

Purpose of Review: Rapid introduction of newly developed drugs in the absence of clear understanding of the pathophysiologic mechanisms behind drug-induced lupus erythematosus (DILE) can sometimes make DILE difficult to recognize in clinical practice. The purpose of this review is to summarize drugs most recently reported to be involved in DILE and discuss the current landscape of diverse mechanisms involved., Recent Findings: A large number of proton pump inhibitor (PPI)-induced subacute cutaneous lupus erythematosus cases have been reported, suggesting a shift over time in the spectrum of drugs implicated in DILE. Twenty-two articles comprising 29 DILE case reports published within the last 2 years are summarized in this review, including 12 (41.4%) systemic DILE. Antitumor necrosis factor (anti-TNF) drugs were the most frequently (41.7%) reported to introduce systemic DILE in these cases. Chemotherapeutic drugs were the most common drug class (54.5%) involved in subacute cutaneous lupus erythematosus, with an observed higher incidence in female patients. Enhanced neutrophil extracellular trap (NET) formation induced by procainamide and hydralazine could be a new mechanism contributing to the pathogenesis of DILE., Summary: The list of drugs implicated in triggering DILE is expanding as new drugs with novel mechanisms of action are being developed. It is important to recognize culprit drugs that may induce lupus erythematosus, as discontinuation usually results in improvement of drug-induced manifestations. Characterizing the mechanisms involved might help better understand the cause of idiopathic autoimmunity.

Purpose: Several antihypertensive medications have been associated with various forms of sexual dysfunction. We present a case report of a premenopausal patient with hydralazine-associated amenorrhea., Methods: The Naranjo adverse drug reaction probability scale was used to assess causality. We also performed a literature search on PubMed to find publications that report hydralazine-associated amenorrhea., Results: The Naranjo scale generated a score of 6, suggesting a probable relationship between amenorrhea and hydralazine therapy. No publications associating hydralazine with amenorrhea were identified., Implications: A probable relationship exists between hydralazine and the development of amenorrhea., (Copyright © 2018 Elsevier Inc. All rights reserved.)

BACKGROUND Hydralazine is an effective antihypertensive agent but may rarely have devastating hepatotoxic effects that are extremely variable, thus making the diagnosis difficult. CASE REPORT We report the case of a 74-year-old male patient who had transaminitis after being started on hydralazine by his cardiologist for poorly controlled hypertension. He had extreme dizziness, nausea, and weakness, which all resolved after discontinuation of hydralazine, and liver function test results also dramatically improved. CONCLUSIONS It is imperative that clinicians be aware of the possible hepatotoxicity of hydralazine and its clinical features so that the medication can be promptly discontinued to help promote liver recovery. This case report will add to the current literature about such infrequent cases of hydralazine-induced hepatotoxicity.

Hydralazine is a direct-acting vasodilator, which has been used in treatment for hypertension (HTN) since the 1950s. While it is well known to cause drug-induced lupus (DIL), recent reports are indicating the emergence of the drug-induced anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis (DIV). Herein, we describe two patients (aged 57 and 87 years) who presented with severe acute kidney injury (AKI), proteinuria, and hematuria. Both were receiving hydralazine for the treatment of hypertension. ANCA serology was positive in both patients along with anti-histone antibodies (commonly seen in drug-induced vasculitis). Renal biopsy revealed classic crescentic (pauci-immune) glomerulonephritis in these patients and hydralazine was discontinued. During the hospital course, the 57-year-old patient required dialysis therapy and was treated with steroids and rituximab for the ANCA disease. Renal function improved and the patient was discharged (off dialysis) with a serum creatinine of 3.6 mg/dL (baseline = 0.9 mg/dL). At a follow-up of 2 years, the patient remained off dialysis with advanced chronic kidney disease (CKD) (stage IIIb). The 87-year-old patient had severe AKI with serum creatinine at 10.41 mg/dL (baseline = 2.27 mg/dL). The patient required hemodialysis and was treated with steroids, rituximab, and plasmapheresis. Unfortunately, the patient developed catheter-induced bacteremia and subsequently died of sepsis. Hydralazine can cause severe AKI resulting in CKD or death. Given this extremely unfavorable adverse-event profile and the widespread availability of alternative anti-hypertensive agents, the use of hydralazine should be carefully considered.

Objective: Aberrant neutrophil extracellular trap (NET) formation has been implicated as a mechanism to induce autoreactivity in individuals at risk of autoimmune diseases. The objective of this study was to assess whether medications implicated in cases of drug-induced autoimmunity (hydralazine and procainamide) and medications less commonly associated with drug-induced autoimmunity (minocycline and clozapine) induce NET formation and/or prevent NET degradation., Methods: Human neutrophils were incubated with the drugs of interest and resultant NET formation was quantified by fluorescent microscopy. The ability of these drugs to interfere with NET degradation by serum nuclei was assessed. Pathways of drug-induced NET formation were studied with pharmacologic inhibitors of reactive oxygen species (ROS), peptidylarginine deiminases (PADs), and muscarinic receptors, and by assessment of intracellular calcium levels by flow cytometry. To determine if NET protein cargo varies by drug stimulus and/or neutrophil source, proteomic analysis of NET lysates induced by specific medications was compared using neutrophils from healthy donors and from patients with autoimmune diseases., Results: Hydralazine and procainamide significantly induced NET formation while minocycline and clozapine did not. None of the medications significantly impaired NET degradation. NETosis induced by these drugs required NADPH oxidase and PAD4 activation. Procainamide triggered NETs via muscarinic receptor engagement on neutrophils, while hydralazine modulated calcium release from intracellular stores. Differences in protein cargo, particularly histone content, were observed in NETs induced by hydralazine and procainamide., Conclusion: Medications commonly implicated in drug-induced autoimmunity trigger NET formation displaying distinct protein cargo, via common and specific pathways. NETosis may play a role in the pathogenesis of drug-induced autoimmunity., (Published 2017. This article is a U.S. Government work and is in the public domain in the USA.)

Background: The aim of this study was to evaluate the use of as-needed (PRN) labetalol and hydralazine [intravenous (IV) or oral] in hospitalized medicine patients for the treatment of severe asymptomatic hypertension and to examine the potential negative outcomes associated with their use., Methods: The electronic health record of 250 medicine patients hospitalized at the University of Colorado Hospital between November 2014 and April 2016 who received at least one dose of PRN IV or oral hydralazine or labetalol were retrospectively reviewed. The primary outcome was to describe the use of PRN antihypertensive medications in this population., Results: A total of 573 PRN doses of antihypertensive medication were administered. Oral hydralazine was the most common (521 doses, 90.9%). A total of 36% of PRN administrations were given for a systolic blood pressure (SBP) <180 mmHg and diastolic blood pressure (DBP) <110 mmHg (cut-point for acute severe hypertension). No serious adverse events were related to PRN antihypertensive administration. Despite receiving at least one PRN antihypertensive medication during hospitalization, 40.8% of patients were not continued on their home antihypertensive medication(s) while hospitalized, and 62.4% of patients did not have their home regimens intensified at discharge., Conclusion: As-needed oral hydralazine is frequently prescribed for acute blood pressure lowering with administration thresholds often less than what are used to define acute severe hypertension. Many patients are prescribed PRN antihypertensive medication instead of being continued on their home regimens, and most patients do not have the intensity of their home regimens increased. Providers need to be educated about the use of PRN antihypertensive medication for the management of severe asymptomatic hypertension in the hospital setting.

Hydralazine-induced small vessel vasculitis is a rare entity with a limited number of cases reported in the dermatologic literature. A characteristic pattern of acral pseudoembolic vesiculopustules with necrosis and ulceration has been suggested along with involvement of the aerodigestive tract, indicating mucosal involvement is an important feature of this disease. We report the case of a patient with hydralazine-induced vasculitis who exemplified this characteristic presentation associated with severe involvement of the aerodigestive tract and gastrointestinal tract bleeding. In addition to the distinctive clinical presentation, the patient's workup revealed the characteristic antineutrophil cytoplasmic antibody (ANCA)-positive serologic profile. Increased recognition of the clinical and serological features of hydralazine-induced small vessel vasculitis may lead to earlier recognition of this disease and decreased time to discontinuation of hydralazine when appropriate. Drug withdrawal is the cornerstone of therapy, and depending on the severity of symptoms, additional immunosuppressive treatment such as corticosteroids may be necessary.

We report a rare case of Hydralazine-induced ANCA associated glomerulonephritis with alveolar hemorrhage in the setting of acute Clostridium Difficile Infection. A 71-year-old Caucasian woman with hypertension, who was being treated with hydralazine 25 mg twice a day for six years, presented to the hospital with diarrhea, nausea, vomiting and anemia. She had acute kidney injury and urinalysis showed proteinuria, dysmorphic RBCs, and rare RBC cast. She was found to have Clostridium difficile colitis which was successfully treated. She became hypoxemic; CT scan findings showed bilateral pulmonary infiltrates. Broncho-alveolar lavage was consistent with pulmonary hemorrhage. Kidney biopsy revealed focal segmental necrotizing and diffuse crescentic glomerulonephritis, pauci-immune type (ANCA-associated). Hydralazine was discontinued and the patient was treated with corticosteroids, intravenous cyclophosphamide and plasmapheresis. To our knowledge, hydralazine-associated low complement in the setting of C-diff infection has not been previously reported. This is considered a potentially life-threatening condition requiring immediate discontinuation of the offending medication and expedited lifesaving measures. [Full article available at http://rimed.org/rimedicaljournal-2016-11.asp].

Objective/background: Autonomic dysreflexia is a potentially life-threatening condition which afflicts a significant proportion of individuals with spinal cord injuries (SCI). To date, the safety and efficacy of several commonly used interventions for this condition have not been studied., Design: A retrospective chart review of the safety of a previously implemented nursing driven inpatient autonomic dysreflexia protocol., Methods: Seventy-eight male patients with SCI who experienced autonomic dysreflexia while inpatient at our Veterans Affairs SCI unit over a 3-1/2-year period were included. The safety of a nursing driven protocol utilizing conservative measures, nitroglycerin paste, and oral hydralazine was evaluated., Outcome Measures: Occurrence of adverse events and relative hypotensive events during all episodes treated with the protocol, and efficacy of attaining target blood pressure for all episodes with protocol adherence and for initial episode experienced by each patient., Results: Four hundred forty-five episodes of autonomic dysreflexia were recorded in the study period, with 92% adherence to the protocol. When the protocol was followed, target blood pressure was achieved for 97.6% of all episodes. Twenty-three total adverse events occurred (5.2% of all episodes). All adverse events were due to hypotension and only 0.9% required interventions beyond clinical monitoring. Of each patient's initial autonomic dysreflexia episode, 97.3% resolved using the protocol without need for further escalation of care., Conclusion: This inpatient nursing driven-protocol for treating autonomic dysreflexia utilizing conservative measures, nitroglycerin paste and oral hydralazine achieved target blood pressure with a high success rate and a low incidence of adverse events.