Unanticipated Death

At about 2:00 am on Thursday, 10/18/07, I called the paramedics to take Pearl to the hospital. She had severe chills, stomach pain, vomiting and loose bowels for about six hours and was too weak and dehydrated for me to take her by auto. They administered a sedative, Versed, then transported her. She arrived at the hospital ER at about 4:00 am. The paramedics informed the hospital ER staff that they had given her inhaled Versed at home.

Upon arrival a blood test showed elevated white blood cells and elevated alkaline phosphatase. Also, she was hypotensive and had respiratory depression. I told the ER staff that Pearl didn’t have the symptoms of hypotension and respiratory depression when I called the paramedics – these were new and unusual for Pearl.

At about 8:30 am the ER doctor initiated an IV drip of Zofran to control nausea and vomiting, and Dilaudid for sedation. At 9:00 am she added Cipro IV, an antibiotic, for potential infection. She ordered a CT scan and chest and abdomen x-rays. Oxygen was administered via loose plastic tubing near her nose. Blood cultures were taken in hopes of identifying the bacterium if that were the cause of Pearl’s distress. A blood culture takes six days for growth and results.

At about 9:00 am it was time for Pearl to receive her daily prednisone medication so I advised the ER doctor. The doctor replied that she had Pearl on Cipro for massive infection and didn’t want to mix hydrocortisone with the Cipro. I advised that Pearl had received both simultaneously a year before when being treated for a shoulder staph infection. I also advised her that Pearl has been on high steroids for nine years and she had to have supplementation at once to avoid loss of circulation to her legs and optic nerve.

The ER Dr advised she would discuss it with another doctor and sent Pearl for the CT scan. Pearl’s rheumatologist was vacationing that week so I telephoned Pearl’s internist to gain his help in getting Pearl some supplemental corticosteroids. His office assistant said she would tell him – I advised her it was urgent. I learned two weeks later that the CT scan and X-rays showed nothing unusual in her stomach and intestines. There was no perforation, no signs of infection or organs inflammation. Pearl still wasn’t given corticosteroids.

At about noon I went home because Pearl seemed to be stable, there was nothing I could do for her at that time. Our daughter was present and I hadn’t had an opportunity to sleep at all during the night and morning. I managed two hours of sleep and returned to the hospital at about 3:00 pm.

Flagyl, an antibacterial medication for potential intra-abdominal infections or systemic blood infections, was given to Pearl at about 1:50 pm. Pearl’s internist advised me later that he came to the ER at about 2:30 pm. The ER nurse offered Pearl two hydrocodone pills at 2:45 pm – she took only one since it was hard to swallow.

The first sign of a fever appeared at 3:58 pm when rectal temperature was measured to be 101.2 degrees (this is equivalent to an oral temperature of 100.2 degrees).

Respiration numbers were declining so the ER staff replaced the oxygen hose with a face mask. The face mask had sharp edges and was very irritating to Pearl’s thin frail skin. She was agitated by it so we tried to hold it slightly off her face to eliminate contact with the sharp edges. At 4:55 pm a pulmonologist sedated Pearl with IV Levophed, Etomidate and Versed. He inserted a breathing tube in her throat to control respiration via a mechanical ventilator, replacing the oxygen mask. The ER doctor advised me at about 4:45 pm that he had started an IV stress dose of 100 mg of hydrocortisone and would repeat it every 8 hours. This is the equivalent of about 25 mg of prednisone which is double Pearl’s daily dose. Two weeks later I saw no reports that confirmed this – the medications administered in the ER were listed by the nurses on duty and hydrocortisone wasn’t listed. Literature states that a stress dose should have been administered upon her arrival at the ER due to her dehydrated condition and need for corticosteroid supplementation.

A Versed drip was started at 5:55 pm then an increased amount at 6:00 pm At about this time the ER staff converged around Pearl – she had lost measurable pulse in her arms and legs. They did some emergency procedures including administering Sodium Bicarbonate at 6:28 pm. This is an electrolyte replenisher and systemic alkalizer; they also administered normal saline. Circulation was restored by 7:00 pm. A significant skin wound in her right shin was noted to have developed and was bleeding. A blood culture was taken of that wound. Follow-up after her death showed no growth three days later and cultures taken earlier that day showed no growth after six days. This indicated she didn’t have a bacterial infection.

Liver, kidneys and lungs were showing signs of trauma. Lipase and amylase were measured at 6:30 pm for signs of pancreatitis – amylase was elevated but lipase was normal. Another IV dose of Versed was administered at 6:47 pm while Pearl was still in shock.

She was transferred to the intensive care unit at 8:00 pm; degradation of systems continued. Blood tests at 6:00 am the next morning (10/19/07) showed significant damage to the liver and kidneys. Lactic acidosis was elevated indicating lung degradation. Her heart stopped at 8:45 am and she was resuscitated. This occurred two more times. The Nephrologist recommended placing a dialysis tube in Pearl to start dialysis since her kidneys were not functioning. 15 minutes after doing the procedure her heart stopped a fourth time – at that point I recommended they not resuscitate and let her be at peace.

In my mind this hospital visit was to be a routine treatment for Pearl’s immediate problem of extreme weakness and dehydration due to vomiting and diarrhea and we would go home the day of admittance. I was not prepared mentally for the events and her death that happened so swiftly. Questions raced through my mind in my disbelief of her trauma and untimely demise. Some of these questions persist and cannot be answered. I requested and eventually received a copy of hospital and doctor’s reports and records. The first batch was obtained on 10/31/07 – some data was obviously missing. Additional data was obtained in two batches later.

Having the benefit of the hospital records I received, including nurses’ logs, Doctors’ reports, test reports, and drug descriptive literature, I have made several observations regarding Pearl’s ER care. It is evident that four additional sedatives were applied to Pearl to overcome the adverse effects of earlier sedatives. Overuse of sedatives and sedative allergy can reasonably explain her swift and unanticipated death.

  1. Versed should not be administered to an elderly dehydrated patient because of the risk of hypotension, respiratory depression and anaphylactic shock. Yet it was administered by the paramedics, the ER pulmonologist consultant, and the two ER doctors. It was administered at home by the paramedics in two bolus doses – a bolus dose should not be administered by inhalation since it cannot be measured. Pearl arrived at the ER with two of the symptoms of hypersensitivity to Versed – hypotension and respiratory depression. The paramedics advised the ER that they had administered Versed to Pearl at home. Arm and leg arteries shut down within the hour after Versed was administered for intubation with two other anesthetics by the pulmonologist. Versed was then administered again by the ER doctor while Pearl was obviously in shock which is contraindicated by Versed application guidelines.
  2. Dilaudid should not have been administered to Pearl in the ER. She already had symptoms of hypotension and respiratory depression. When used with other sedatives respiratory depression, hypotension and profound sedation or coma may occur. Dilaudid contains a sulfite which Pearl was allergic to – the ER was aware of this allergen. A sulfite can cause allergic-type reactions including anaphylactic symptoms and life-threatening episodes in susceptible people. Drug warnings include concern for the use of Dilaudid by patients who have adrenocortical insufficiency. Pearl had adrenocortical insufficiency because of using high dose levels of corticosteroids for suppression of giant cell arteritis inflammation for the previous nine years. The ER doctor was aware of this.
  3. Hydrocodone should not have been offered for pain relief by the ER nurse. It added to the burden of the symptoms that Pearl arrived with at the ER. It can cause vomiting, respiratory depression, acute abdominal distress. She was elderly and debilitated and needed corticosteroid supplementation as would an Addison’s disease patient - these are contraindications for hydrocodone.
    4.
  4. Levophed should not have been administered by the ER pulmonologist. It is a potent vasoconstrictor that can cause ischemic injury. Pearl’s leg arteries had been restricted and blocked by giant cell arteritis inflammation for eight years and were susceptible to any type of vasoconstricting medication. Also, her one good eye was at significant risk for ischemic injury (blindness) from such a medication. Within the hour after Levophed was administered pulse to Pearl’s arms and legs could not be measured, indicating possible anaphylactic shock.
  5. Etomidate should not have been administered by the ER pulmonologist. It can contribute to hypotension and vasoconstriction of arteries. The lack of pulse in her extremities occurred within the hour of administering this medication and those mentioned above. At some time during the evening while in the ER Pearl appeared to be comatose. Her eyes were wide open but not responsive.
  6. Pearl had been taking Darvocet N100 three times a day at home – her last dose likely was at dinner time. Darvocet has an opiate component which is an added risk when using the sedatives listed above. Drug interactions produced an indeterminate effect on her system. The paramedics and the ER doctor were aware of this.
  7. The actions of the above medications produced significant internal system stress. Cortisol is needed to fight stress. Pearl’s glands weren’t making cortisol thus she had an urgent need for supplementary corticosteroids in the ER. The stress started to develop at home during six hours of vomiting and diarrhea. Stress increased with Versed sedation by the paramedics, and increased with Dilaudid and hydrocodone administered in the ER. Stress may have culminated in shock upon administration of Levophed, Etomidate and more Versed by the pulmonologist.
  8. I saw no mention of pancreatitis in the ER reports, yet the ER doctor told me the morning of admittance that there was evidence of it. I erroneously assumed that pancreatitis was determined by the CT Scan but it is not mentioned in the CT Scan report. The X-rays of the abdomen and chest taken that morning found no evidence of a problem. Elevated WBC and Alkaline Phosphatase occurred when Pearl was diagnosed with Giant Cell Arteritis nine years earlier. Adequate prednisone dosing brought WBC down significantly and Alkaline Phosphatase was brought back to normal at that time. Their elevation in the ER could have reflected either uncontrolled Giant Cell Arteritis or, as the ER doctor suspected - systemic infection due to pancreatitis. Since Pearl didn’t have a fever upon admittance systemic infection is unlikely.
  9. The ventilator tube placed in Pearl’s throat was resting on the carina of the lungs, possibly blocking good respiration of her lungs. The carina is the shelf where the lungs separate. This may have caused lactic acidosis to form as noted by the Nephrologist. The ventilator tube misplacement was noted twice by the X-ray doctor but wasn’t acted upon in the ER after he first brought it to their attention. The tube was placed in Pearl within the hour before pulse diminished in arm and leg arteries.

Some additional observations or questions potentially related to either her final moments in the hospital ER or routine care leading up to the final hospital visit follow.

  1. Pearl was taking 18 prescription medications on an on-going basis when stricken on 10/17/07 at about 8:00 pm, two hours after a dinner of poached salmon and salad at home. She had what appears to have been a similar episode eight days earlier on 10/9/07 from which she recovered without assistance within 24 hours. The episode on 10/9/07 occurred two hours after receiving an anesthetic injection of lidocaine followed by a corticosteroid injection of depomedrol in her right knee which was swollen with fluid. I suspect she had an allergic reaction to the lidocaine. Iodine in the salmon on 10/17/07 may have been an allergen or difficulty digesting the fish oil may have set off her distress leading to the ER visit.
  2. Two medications suspected by some ER/ICU doctors of being contributors to her demise are prednisone and methotrexate (MTX). Pearl started taking MTX two months before the ER visit and didn’t exhibit any distress from it. She had taken MTX successfully for a year in 2001. She had been taking prednisone daily since December, 1998. Her dosage level at this time was 12 mg/day.
  3. Fatal bone marrow suppression may have been caused by the combination of prednisone and MTX. Pearl had several symptoms of bone marrow suppression and nephrotoxicity – namely nausea, vomiting, diarrhea, and chills both on 10/9/07 and 10/18/07.
  4. Altace, an ACE inhibitor, combined with MTX increases liver injury risk according to drug information - did we monitor hepatic function adequately?
  5. Boniva and MTX increase the severity of renal impairment due to additive effects on the kidney according to drug information. Did we monitor renal function and serum electrolytes adequately?
  6. Patients undergoing methotrexate therapy should be closely monitored so that toxic effects are detected promptly. Baseline assessment should include a complete blood count with differential and platelet counts, hepatic enzymes, renal function tests, and a chest X-ray according to drug information. We didn’t check serum content of MTX, liver enzymes, urine or chest Xray as a baseline, or repeat often while on MTX. Her CBC and CMP were measured monthly.
  7. Pearl’s gallbladder was removed in 1989 because stones were present in the bile duct. Could the duct have been impaired and complicated the fluid flow of pancreatic secretions, interfering with the digestive process?
  8. MTX can cause pancreatitis according to drug information. Pancreatitis begins when the digestive enzymes become active inside the pancreas and start "digesting" it. Symptoms of acute pancreatitis include pain in the abdomen, nausea, vomiting, fever, and a rapid pulse. People with chronic disease often lose weight, even when their appetite and eating habits are normal – Pearl lost 25 lbs. in the last 6 months which was not normal. If pancreatitis were present Pearl should have been taking pancreatic enzyme supplements and eating a low-fat diet but we weren’t knowledgeable about this potential condition. Pearl did not have fever until 4:00 pm in the ER so the pancreatitis symptom of fever was not present when pancreatitis was suspected by the ER doctor early that morning.
  9. Pearl had high triglycerides (325) that the Cardiologist was concerned about but she couldn’t tolerate his prescribed medication, Tricor. It caused blurry vision on 7/12/06 so it was discontinued. He kept Pearl on Toprol-XL, a beta blocker, though literature says beta blockers can cause a massive increase in triglycerides. Should Pearl have remained on a beta blocker since that may have been the cause of the high triglycerides?
  10. Pearl must have been severely dehydrated from repeated vomiting. Severe cases may cause dehydration and low blood pressure. The heart, lungs, or kidneys may fail. If bleeding occurs in the pancreas, shock and sometimes even death follow. There was no evidence of internal bleeding. Vomit and stool were clear of blood, and CT Scan and X-rays didn’t show bleeding.
  11. Medications that Pearl may have been adversely affected by, after considering the information above:

The combined effects of methotrexate and other medications may have made the kidneys and liver – and possibly the pancreas – more vulnerable to a systemic invasion. The arguments against pancreatic involvement and severe infection are:

Perhaps it was unfortunate that Pearl was taking MTX, Darvocet, Toprol-XL and Lasix. MTX had the promise of allowing eventual prednisone dose reduction - recent literature supported that promise, as did her use of it in 2000 for 11 months. While on MTX she should have had more diagnostic tests for kidney, liver and pancreas function. Lung X-ray and MTX serum levels should have been monitored in addition to the monthly CBC, CMP, C-rP and sed rate tests. Had that been done we would have less to speculate about her death.

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