Critical Review of Fact Finding Report on the Death of Shri Alok Pandey By Ashok Gupta [email protected] September 19, 2016

Director IIT Kanpur set up a committee consisting of 3 physicians and 2 student observers to prepare a Fact Finding Report of the death of Shri Alok Pandey, a PhD student. Shri Pandey died on August 8, 2016.The Committee was set up on August 9, 2016. The report was based on the deliberations from 2Pm till 7PM on August 10, 2016. These deliberations included interrogations and statements of two Health Centre attending physicians, 3 staff nurses, and 2 students that accompanied Shri Pandey in the ambulance. One of the students interrogated also walked with Shri Pandey from his lab to the Health Centre. Recording of these interrogations/statements were not included in the report even though the cover letter to the report says they are. The report was submitted to the Director on August 17, 2016 [1]. Presented below is a critical review of the Fact Finding Report [1].

CONFLICT OF INTEREST Two of the three physicians on the Fact Finding Committee, Dr. S. S. Singhal (Cardiologist) and Dr. Rakesh Chandra (Medicine) are associated with the IITK Health Centre and are financially benefited from it. At the Health Centre, Dr. Singhal runs Cardiology Clinic. Dr. Chandra runs Medicine Clinic and is also Medical Advisor to the Health Centre [2]. I believe this constitutes conflict of interest and their report should be viewed in that light. To the best of our knowledge, Dr. Mohamad Ahmad (Cardiologist), the 3rd physician on the committee, is not associated with the Health Centre and is not financially linked with IITK. All three physicians work at GSVM Medical College and are, therefore, colleagues.

NO REFERENCE TO THE POST-MORTEM REPORT As per the report titled, “Summary of Major Events during August 8 to 17, 2016” shared by the Alumni Association Secretary about the events surrounding Shri Pandey’s death we learned that in the afternoon of August 9, 2016, the post mortem had been completed in the city [3]. It is strange that the Fact Finding Report prepared on the basis of August 10 deliberations, a day after the post-mortem, had nothing to say about what was found in the post-mortem and how its findings relate to the findings of the committee. In fact, the report submitted a week later on August 17 is completely silent about the post-mortem. Why?

VITAL SIGNS OF THE PATIENT -- SHRI ALOK PANDEY It is customary that when a patient comes to see a physician, his vital signs are taken and recorded. The patient, Shri Alok Pandey, walked with a friend from his lab/office to the Health Centre and should have been in a position to answer physician’s questions unless his vital signs were never taken. The Fact Finding Report does not provide any indication whether any of the following were asked of the patient and what they were: Age of the patient Height/Weight Blood Pressure Heart Rate Body Temperature Current Medications patient is taking Known allergies We wonder why investigators did not look into the vital signs of the patient and made a note of them in their report. And if they were never taken, why did they not question the attending physicians for this negligence.

ADMINISTRATION OF VOVERON INJECTION Voveron is a brand name for what is known in the medical literature as Diclofenac. In the rest of the report we will use the term Diclofenac instead of Voveron. The Fact Finding Report does not provide even the basic information such as the dosage of Diclofenac injection administered on Shri Pandey. Where in the body the injection was given? At what temperature the injection was stored at the Health Centre? Was the injection used beyond its date of expiry? Our research suggests that: the injection should be given in buttock, it should not be stored at temperature >250C, expired injection should not be used, and it should be given with food or immediately after the patient has eaten. The Fact Finding Report does not indicate if any of these questions were asked/investigated. Why?

DID SHRI PANDEY DIE DUE TO DICLOFENAC INJECTION? The committee attributed cause of death of Shri Pandey to “severe heart attack leading to acute heart failure [1].” However, the committee failed to address the most important question, “Why did a young student like Shri Pandey (let’s say 26 years old since we are not told his real age) with no history of high blood pressure, diabetes, or cardiac disorder suddenly had a severe heart attack?” I will address this question based on medical research. A physician friend researched the case of Shri Pandey. Based on his research, it is very likely that Shri Pandey had anaphylaxis (a severe, potentially life-threatening allergic reaction) from Diclofenac injection. Since the probable anaphylaxis was not recognized by the attending physicians and no anti allergic medicines were administered, it led to severe heart attack.

Diclofenac has been associated with Kounis syndrome, a mast-cell mediated anaphylaxis which can cause fatal ST-segment elevation cardiac events. Kounis syndrome was first described in 1991 as “allergic angina syndrome” or “allergic myocardial infarction.” Myocardial infarction (MI) (i.e., heart attack) is the irreversible death (necrosis) of heart muscle secondary to prolonged lack of oxygen supply (ischemia). Please see two articles attached selected for the Indian context [4, 5]. Diclofenac is the most commonly reported non-steroidal anti-inflammatory drugs (NSAIDs). NSAIDs are one of the most commonly implicated class of medications causing anaphylaxis [5]. Because of the wide usage of NSAIDs, physicians should have knowledge of this syndrome and should be prepared to deal with it in a timely fashion. How serious of anaphylaxis threat is posed by Diclofenac? In a research article, fifty-four cases of anaphylaxis were analyzed and it was found that the most common causative drug among the 35 drugs that caused anaphylaxis was diclofenac (6 cases, 11.11%). Other commonly implicated drugs were atracurium (7.41%), vecuronium (5.56%), ranitidine (5.56%), fentanyl (3.70%), midazolam (3.70%), ceftriaxone (3.70%), artesunate (3.70%), iron sucrose (3.70%) and gelofusine (3.70%) [5]. Can young people like Shri Alok Pandey have Diclofenac induced anaphylaxis? On the basis of the 54 cases reported, the most vulnerable age group is 21-39 years. Shri Pandey would fall in this group. The age group distributions of the 54 cases of anaphylaxis was 0–20 years (25.93%), 21–39 years (42.59%), 40–60 years (20.37%) and >60 years (11.11%) [5]. Can someone have heart attack due to anaphylactic reaction? Case of a 64 years old patient is presented in [4] that developed acute myocardial infarction following a diclofenac sodium-induced anaphylaxis. The patient did not have any previous coronary artery disease. Ten minutes thereafter, the patient developed chest pain and pruritus over the lip along with redness and wheal over the site of injection [4]. In the analysis of 54 cases [5], cardiovascular features dominated (98.15%) the systems involved in anaphylaxis followed by respiratory (81.48%), cutaneous (72.22%) and gastrointestinal symptoms (9.26%). Almost 50% cases showed simultaneous involvement of cardiovascular, respiratory and cutaneous systems. High mortality and morbidity is observed for anaphylactic reactions [5]. Therefore, anaphylactic reaction commonly manifests itself as chest pain.

How quickly the anaphylactic reaction takes place? Again, the analysis of 54 cases of anaphylactic reaction reveals that many reports described the incubation period as “Immediate/soon after the administration of the drug (25.93%)” and “within few min (11.11%).” It was within 1-5 min in 18.52%, >5-30 min in 24.07%, >30 min in 11.11% and not stated in 9.26% cases [5]. It is clear that the time is of essence during the anaphylactic reaction induced by Diclofenac. However, in Shri Pandey’s case, valuable time was lost in preparing the patient for ECG and waiting for Dr. Nigam’s arrival instead of administering anti-allergic medicines against anaphylactic reaction.

The following chart summarizes, what might have happened in case of Shri Pandey: Diclofenac (Voveron) injection administered

Anaphylactic reaction occurs

Heart Attack

No life-saving intervention from physicians to treat anaphylactic reaction

Heart Failure

Patient sent to hospital in an ill-equipped ambulance

COULD SHRI PANDEY HAVE BEEN SAVED? Yes, if the probable anaphylaxis to Diclofenac had been recognized and treated. Attending physicians failed to recognize signs of allergic reaction induced by Diclofenac. Although Shri Pandey died of heart failure, it was caused by severe stress to the heart due to failure to treat anaphylactic reaction induced by Diclofenac. It is expected that physicians should know that Diclofenac has been associated with Kounis syndrome which was first described in 1991. Physicians should have also known that anaphylactic reaction occurs quickly, most likely among young patients, and it commonly manifests itself as chest pain.

Medical literature provides treatment of anaphylaxis with adrenaline (1 in 10,000) and 10 mg chlorpheniramine maleate IV, along with 125 mg of methyl prednisolone [4]. Corticosteroid, antihistaminic, inotropes, bronchodilators, H2 receptor antagonists and vasopressors are also suggested [5]. TRIP TO THE HOSPITAL IN ILL-EQUIPPED AMBULANCE The Fact Finding Report is silent on how long did it take for the ambulance to arrive at the hospital once it left Health Centre, what type of monitoring devices were on the ambulance, if anyone was actually monitoring Shri Pandey’s condition, was there any medically trained person on the ambulance, and when did Shri Pandey actually die since he was declared dead on arrival in the hospital. There are also allegations that in the Health Centre, Shri Pandey was made to walk to the ECG room despite showing signs of cardiac distress and he most probably died in the ECG room itself and yet the Health Centre staff put on an oxygen mask to the body and sent him to the city in an ambulance only to be declared dead. This needs to be investigated. The only issue that the report points out is that the patient should have been given frusemide injection before being put on the ambulance. The report, however, justifies non-administration of this injection on the lack of expertise and experience available in a Primary Health Centre [1]. What kind of expertise or experience is required to administer an injection which was not available in Health Centre? We find this defense with little merit unless the patient was already dead when being put on the ambulance and the thought of this additional step seemed superfluous.

RECOMMENDATIONS The Fact Finding Report contains few recommendations going forward. These are good recommendations however, they are silent in many critical areas. We would like to make additional recommendations: 1. All physicians at the Health Centre be required to update their medical knowledge by attending continuing education programs every year. From the case of Shri Pandey it is clear that the attending physicians did not recognize that the patient suffered from diclofenac induced Kounis syndrome – a syndrome which was first reported in 1991! We wonder what other areas these physicians might be deficient in. 2. We have no proof, but allegations of nepotism in hiring physicians, physicians getting kick-backs from medical representatives, and overprescribing medicines to boost their cut from medical stores have been posted on social media. We recommend thorough investigation of such practices. 3. If there is no performance appraisal system in place for the physicians in Health Centre, it should be immediately implemented. 4. Inventory of all medicines/injections in the Health Centre should be checked for their dates of expiry, genuineness, and if they are being stored as recommended. 5. It should be mandatory that vital signs of all patients be taken and recorded after check in. To ensure completeness, a check list should be prepared which should be completed by all physicians at every encounter. 6. The ambulance is not a thela gaddee for transporting bodies from Health Centre to the City Hospitals; it should be treated as a mobile emergency clinic. Those operating the vehicle should be paramedics (trained to do medical work, especially emergency first aid, but is not usually a fully qualified physician) and not just drivers. Ambulance should be well equipped. Please see guidelines for ambulances developed by American College of Surgeons [6]. Similar Guidelines may be available in Indian context.

REFERENCES [1]

Fact Finding Report of the Death of Shri Alok Pandey https://goo.gl/nQ2Cs2

[2]

Action Taken Report on the Recommendations of the Fact-Finding Committee constituted for looking into the tragic demise of Shri Aftab Alam, Principal Research Engineer, Computer Center

[3]

Summary of Major Events during August 8 to 17, 2016 http://www.iitkalumni.org/files/Summary_Events_Occurred_Institute.pdf

[4]

Indian Journal of Anaesthesia, 2013 May 57(3)282-4, Tianna AK, Tomar GS Longul CS, Kapour MC "Kounis syndrome resulting from anaphyllaxis to diclofenac".

[5]

Indian J. Critical Care Med. 2014 Dec 18(12)796-806, Tejas K Patel, Parvati B Patel, Manish J. Barvaglia, CB Tripathi "Drug Induced Anaphyllaxis Reactions in Indian Population: a Systematic Review".

[6]

Guidelines for Ambulances developed by American College of Surgeons https://www.facs.org/~/media/files/quality%20programs/trauma/publications/ambulance.ashx