Second-degree Heart Block Caused by Itolizumab-induced Infusion Reaction in COVID-19

How to cite this article: Kumar A, Kumar N, Lenin D, Kumar A, Ahmad S. Second-degree Heart Block Caused by Itolizumab-induced Infusion Reaction in COVID-19. Indian J Crit Care Med 2021;25(4):474–475.

Sir,Itolizumab, an anti-CD6 humanized IgG1 monoclonal antibody, binds to domain-1 of CD-6 that is responsible for priming, activation, and differentiation of T-cells.^[1] It significantly reduces T-cell proliferation along with substantial downregulation of the production of cytokines/chemokines.¹ It was approved for moderate to severe chronic plaque psoriasis in 2013. However, it has recently been approved by the Drug Controller General of India for emergency use in India for the treatment of cytokine release syndrome in moderate to severe acute respiratory distress syndrome patients due to COVID-19.² Here, we report a case of life-threatening infusion-related hypersensitivity reaction of itolizumab.A 65-year-old male COVID-19 patient got admitted to the intensive care unit (ICU) with complaints of shortness of breath and cough without any history of known disease. However, the baseline electrocardiogram (ECG) done in the ICU was suggestive of left bundle branch block (LBBB) (Fig. 1A). The patient was supported through noninvasive ventilation (NIV) and was started on remdesivir, dexamethasone, low-molecular-weight heparin, antibiotics, and other supportive treatment as per our institutional standard protocol. The patient was maintaining on continuous positive airway pressure mode of NIV with a fraction of inspired oxygen (FiO₂) of 0.5 on the third day of ICU admission. Among the laboratory markers, the total leucocyte counts were raised (12,000/μL) with decreased lymphocytes (3.2%) and increased inflammatory markers (CRP, 320 mg/L; D dimer >20 μg/mL; LDH, 1694 U/L; IL6, 329 pg/mL). Serum electrolytes, renal function tests, liver function tests, and arterial blood gases were within acceptable limits. The patient was hemodynamically stable with a respiratory rate of 30 to 35/minute and a PO₂/FiO₂ ratio of 140. After taking informed written consent, inj. itolizumab was planned in this patient because of the increasing severity of the disease along with increased inflammatory markers. Inj. hydrocortisone 100 mg IV and inj. pheniramine 30 mg IV were given 30 minutes before itolizumab infusion. And 100 mg of itolizumab (Alzumab-L, Biocon Biologics) was diluted to 250 mL with normal saline and was started at 25 mL/hour. After about 20 minutes of infusion, the patient started complaining of shivering, sweating, and impending doom. The patient had sudden bronchospasm, and oxygen saturation dropped to 90%. ECG showed second-degree AV nodal block with an increased blood pressure of 180/110 mm Hg (Fig. 1B). The drug was immediately withdrawn and the patient was given a repeat dose of hydrocortisone and pheniramine along with other supportive measures. After sometime patients became alert and their respiratory symptoms were relieved. However, the second-degree heart block in ECG was persistent. ECHO was normal and troponin I was within normal limits while there was a slight increase in CPK-MB. The patient was observed closely and the ECG reverted to its previous state only after 24 hours. The patient was weaned from the ventilator in due course of time and put on face mask on the eighth day of stay.Open in a separate windowFigs 1A and B(A) Baseline ECG showing LBBB; (B) ECG showing second-degree AV nodal block after infusion reactionMost infusion reactions related to monoclonal antibodies are IgE mediated and are mild (grade 1 or 2) in nature.³ The incidence of severe (grade 3 or 4) reactions is generally low. The reported infusion-related reactions to itolizumab are chills/rigors (common), nausea, flushing, urticaria, cough, hypersensitivity, pruritus, rash, wheezing, dyspnea, oxygen desaturation, dizziness, headache, and hypertension. In our case, itolizumab infusion leads to a grade 4 reaction causing a persistent second-degree heart block for about 24 hours. Among the monoclonal antibodies, rituximab is most notorious for causing infusion reactions.⁴ There are only a few reports of cardiac arrhythmias (monomorphic VT, supraventricular tachycardia, trigeminy, and irregular pulse) during therapeutic infusion of rituximab,⁵ and there is no reported case of cardiac arrhythmia during itolizumab infusion. In our case, the patient was having LBBB and was on a QT prolonging drug (remdesivir), which might be a predisposing factor for the occurrence of second-degree heart block during infusion reaction. Premedications (e.g., antipyretics, antihistamines, and steroids) are recommended before the administration of some chemotherapeutic agents and monoclonal antibodies. These drugs should never be given as IV bolus and should always be given slowly in an infusion. Baseline assessments including vital signs and cognition should be documented carefully before the start of treatment and all the emergency equipment and drugs should be kept ready. Grade 3 and 4 reactions should be managed promptly with epinephrine, antihistaminics, and steroids along with other symptomatic supportive measures. As itolizumab is approved for emergency use in COVID-19, risk-benefit ratio should be assessed before prescribing this and should be explained before taking consent for infusion.The patient provided written informed consent for the publication.     

Risk assessment of Pakistani individuals for diabetes (RAPID)

ObjectiveTo develop and evaluate a risk score to predict people at high risk of developing type 2 diabetes in Pakistan.MethodologyCross sectional data regarding primary prevention of diabetes in Pakistan. Diabetes risk score was developed by using simple parameters namely age, waist circumference, and family history of diabetes. Odds ratios of the model were used to assign a score value for each variable and the diabetes risk score was calculated as the sum of those scores.ResultsWe externally validated the score using two data from 1264 subjects and 856 subjects aged 25 years and above from two separate studies respectively. Validating this score using the first data from the second screening study gave an area under the receive operator characteristics curve [AROC] of 0.758. A cut point of 4 had a sensitivity of 47.0% and specificity of 88% and in the second data AROC is 0.7 with 44% sensitivity and 89% specificity.ConclusionsA simple diabetes risk score, based on a set of variables can be used for the identification of high risk individuals for early intervention to delay or prevent type 2 diabetes in Pakistani population.     

The Duboisia Genus,Australian Aborigines and Suggestibility

Abstract

Plant hallucinogens, such as those of the Duboisia genus called pituri, have been used by tribal elders in Australian aboriginal populations to create managed states of consciousness, to provide their youth with a fast-paced educational experience, and to inculcate values, beliefs and religious tenets. Use of the suggestible states created by such substances (particularly in pubertal initiatory rituals marking the transition to manhood) are part of this process, which contributes to cultural cohesiveness and survival; their effectiveness is due to the unique ability of the biochemical properties of the plant to evoke suggestibility in those who ingest them. This article draws on research about suggestibility as a psychological characteristic of altered states of consciousness as well as a normal human psychological phenomenon, and examines in great detail the use of the pituri plant, deriving data from a 100-item bibliography generated by the Australian Institute of Aboriginal and Torres Strait Islander Studies in Canberra. Botanical/chemical data on use of the Duboisia genus up to the end of the nineteenth century is examined, as well as the way in which this hallucinogen was utilized as a “psychotechnology.”     

Prevalence of HOXB13 mutation in a population of Ashkenazi Jewish men treated for prostate cancer

We performed a retrospective analysis of germline DNA samples from Ashkenazi Jewish men and a comparison group of non-Ashkenazi men treated for prostate cancer at our institution to determine the prevalence of HOXB13 G84E mutation in prostate cancer patients of Ashkenazi Jewish heritage, an ethnic group common to the New York City area. Patients were genotyped for G84E using a TaqMan assay (Applied Biosystems). Positive cases were confirmed using Sanger sequencing. Median age at prostate cancer diagnosis was 68 years for 889 Ashkenazi Jewish patients, 64 years for 920 non-Ashkenazi Jewish patients. The median follow up was 9 years for Ashkenazi Jewish patients and 8.8 years for non-Ashkenazi Jewish patients. Only 4 patients were found to be heterozygous carriers of G84E. They were all of non-Ashkenazi Jewish ancestry and were diagnosed at 70, 66, 78, and 49 years of age. Two of them presented with high-risk prostate cancer. The prevalence of G84E in the non-Ashkenazi sample was 0.4 %. HOXB13 G84E mutation was not observed in prostate cancer patients of Ashkenazi Jewish ancestry treated at our institution. Screening for G84E, therefore, may be unnecessary in Ashkenazi Jewish men if these results are validated by other studies.     

Road towards promoting patient safety practices among hospital pharmacists: Hospital-based baseline patient safety culture assessment cross-sectional survey

Patient safety is a fundamental aspect of a healthcare system. The aim of this study was to assess the perception and determinants of the patient safety culture of pharmacists in hospitals, in Riyadh, Saudi Arabia.A survey was conducted with pharmacists in the pharmacies of governmental, /military and private hospitals in Riyadh, Saudi Arabia. The pharmacy survey on patient safety culture questionnaire developed by Agency for Healthcare Research and Qualtity, a hard copy was distriuted to the pharmacists. The positive response rate (RR) was calculated and compared across hospitals using a chi-square test. The predictors of patient safety grades were identified using the generalized estimating equation. The data was analyzed using SAS.A total of 538 questionnaires were distributed, of which 411 responded (RR 76.4%). Of the participants, 229 (56%) were females. The majority 255 (62%) were in the 18 to 34 years age range, and 361 (88%) had a bachelor''s degree. The majority of the sample 376 (92%) was a pharmacist. The Positive RR (PRR) ranged between (25.6%–74%). The highest PRR was observed in teamwork (74.4%), followed by ‘staff, training and skills’ (68%), and ‘organizational learning continuous improvement’ (66%). The lowest PRR was observed in ‘staffing, work pressure, and pace’ (25.5%). Comparing the PPR of the various healthcare sectors, the governmental hospitals scored the highest in all patient safety domains. Generalized Estimating Equation analysis showed that with increase in scores of all patient safety culture domains increased the likelihood of reporting a better patient safety grade, whereas respondents’ demographic characteristics had no effect except the working experience years 6 years and above had odds of poor reporting of the patient safety grade (odds ratio = 2.54, 95% confience interval (1.543, 4.194), (P = .0003).The grades achieved in the various domains of patient safety culture by pharmacists in Riyadh are below the expected standard. The highest scores were achieved in teamwork, with the lowest scores in staffing, work pressure and pace. Overall, pharmacists in government hospital settings have a better perception of patient safety than their peers in other settings. These results provide the baseline evidence for developing future interventional studies aiming at improving patient safety culture in hospital pharmacy settings.     

Reproducibility of systemic hemodynamics in stable chronic hemodialysis: a pilot study

OBJECTIVE: Hemodynamic measurements are important in the understanding of hemodialysis (HD) hypertension and intradialytic hypotension. The reproducibility of hemodynamic measurements in HD patients is not known and is the objective of this report. METHODS: We enrolled 13 male patients (mean age 63+/-13 years) on stable chronic HD. Blood pressure (BP) and hemodynamic variables were obtained with a pulse dynamic technology device. Measurements were taken before and after HD, in the supine and standing positions over a 2-week period. RESULTS: Ranges for the average intraindividual standard deviation for each hemodynamic variable before and after HD in both supine and standing positions were: 8.3-14.5 mmHg for oscillometric systolic BP; 4.1-10.7 mmHg for oscillometric diastolic BP; 10.7-14.5 mmHg for manual systolic BP; 5.4-8.8 mmHg for manual diastolic BP; 131.4-188.9 mmHg/s for left ventricular dP/dtmax; 0.17-0.27 L/min/m for cardiac index; 142.4-222.6 dynes/s/cm for systemic vascular resistance; 0.59-1.13%/mmHg for brachial artery distensibility; and 0.09-0.15 ml/mmHg for systemic vascular compliance. Repeated measures analysis of variance results showed no significant variability in measures. Intraclass correlation coefficient ranges were 0.58-0.72 for oscillometric systolic BP, 0.46-0.83 for oscillometric diastolic BP, 0.41-0.62 for manual systolic BP, 0.57-0.84 for manual diastolic BP, 0.10-0.78 for left ventricular dP/dtmax, 0.63-0.84 for cardiac index, 0.47-0.80 for systemic vascular resistance, 0.40-0.84 for brachial artery distensibility, and 0.62-0.88 for systemic vascular compliance. No correlation was observed between interdialytic weight gain and hemodynamic variability. CONCLUSION: In this pilot study, hemodynamic variables have acceptable reproducibility in chronic stable HD patients. Our results are relevant to the use of hemodynamic monitoring in HD practice and research.