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Impressum

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. 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. The CT scan and x-rays showed nothing unusual in her stomach and intestines. There was no aortic aneurysm, intestinal perforation, internal bleeding, signs of infection or organs inflammation. All organs appeared normal except spleen and kidneys were atrophic. Urinalysis was normal. Pearl still wasn’t given corticosteroids. Pearl still wasn’t given corticosteroids.

At about noon I went home because Pearl seemed to be stable, there was nothing I could do at that time for her 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 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. I saw no reports that confirmed this – the medications administered are listed by the nurses on duty and hydrocortisone isn’t listed.

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.

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 taken 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, tests 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 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. 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 and CT Scan showed organs, other than spleen and kidneys, were normal with no intestinal perforation or bleeding evident systemic infection was 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. Comparisons of blood test reports between 10/15/07 when typical and 10/18/07 when admitted to ER show:

• Kidneys were degrading between 10/15/07 and when measured in the ER on 10/18/07. Bun 29 on 10/15/07, was 37 in ER; Creatinine 1.5, was 2.0 in ER. BUN normal is 5-25; Creatinine is .6-1.2.

• Liver function was degrading: AST 26 on 10/15/07, 51 in the ER; ALT 41, was 51 in ER; Alk Phos 47, was 192 in ER. Normal ranges are: AST 10-40; ALT 4-42; Alk Phos 30-120.

• Infection or inflammation was present: WBC 14.7 on 10/15/07, 22.5 in ER. WBC had not been >20 since the first two weeks of Pearl’s treatment of Giant Cell Arteritis and Polymyalgia (GCA/PMR) in 12/98. It had always been above normal in those nine years except for one reading in March, 2003, when it was 10.3. The normal range for WBC is 4.4 – 10.5.

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 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.
3. Drug info advises that Darvocet and MTX increase risk of liver damage – should bi-monthly biopsies have been done?
4. Prilosec should have been stopped several days before starting MTX according to drug information but was stopped two days after. This may be insignificant however it could have added to the MTX serum load.
5. Pravastatin was stopped one day after starting MTX – it should have been stopped before according to drug information. This may be insignificant but may have contributed to some liver trauma.
6. 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.
7. Altace with MTX increases liver injury risk according to drug information - did we monitor hepatic function adequately?
8. 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?
9. 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.
10. Pearl’s gallbladder was removed in 1989 because stones were in the bile duct. Could the duct have been impaired and complicated the fluid flow of pancreatic secretions, interfering with the digestive process?
11. 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.
12. 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 ?A CT Scan at 9:30 am shortly after admittance to the ER showed her pancreas was normal.
13. 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.
14. Medications that Pearl may have been adversely affected by, after considering the information above:

• Darvocet – acetaminophen component affects kidney function. This was taken for pain; Ultracet was an alternate but she insisted on the Darvocet;

• Boniva – contributes to kidney injury. This was taken for osteoporosis while taking prednisone;

• Methotrexate – can cause pancreatitis. It was taken for its steroid-sparing potential;

• Toprol-XL – contributes to hypertriglyceridemia and vascular constriction. The Cardiologist liked it for her heart;

• Allegra-D – pseudoephedrine component contributes to vascular constriction. Pearl insisted she needed it to prevent chronic coughing – it was effective in stopping a severe gagging type of cough;

• Lasix – dehydration can contribute to pancreatitis. Pearl liked it because it kept her legs/ankles thin.

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:

• Pearl had chills, not fever;
• lipase and amylase – markers for pancreatitis when highly elevated - weren’t measured on arrival to support the ER’s initial diagnosis of pancreatitis;
• CT Scan showed nothing noteworthy around the pancreas or anywhere else;
• X-rays of the abdomen and chest showed nothing unusual.

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.

Cause of Pearl’s Death

The cause of death is listed on the death certificate and the hospital doctor’s report. I disagree with both and provide my own conclusions based on the analysis reported above.

Florida Certificate of Death: Septic shock, multiple organ failure

Hospital ER Physician’s Report:

Septic shock of unclear etiology, Shock liver, Acute renal failure, History of Giant Cell Arteritis, Polymyalgia rheumatica, Hypertriglyceridemia, Hypertension, Spastic colon, Pancreatitis, Gastroesophageal reflux disease, History of cerebrovascular accident related to Giant Cell Arteritis.

James’ Conclusions:

The death certificate and physician’s report list septic shock. There are many types of shock – septic reflects systemic disease which is speculative. Because she had no fever, the CT scan showed no problems and lipase was normal. Lack of fever upon admittance makes systemic disease unlikely. GCA and PMR, while historical, aren’t life-threatening illnesses when properly managed by prednisone. Hypertriglyceridemia leads to liver degradation but isn’t life-threatening in a traumatic manner. Pancreatitis was speculative and unlikely because she had no fever. Spastic colon and GERD without ulceration can cause pain but not death. Pearl’s blindness in one eye, the cerebrovascular accident referred to, has no significance relating to distress in the ER.

After consideration of the information available regarding management of her distress I believe her demise was due to a combination of:

• Anaphylactic or Endocrine shock or both. Anaphylactic shock was brought on by hypersensitivity to or the compounding effect of the five sedatives administered by the paramedics and the ER staff. Endocrine shock resulted from lack of administration of corticosteroids in a timely manner by the ER staff for a patient with adrenocortical insufficiency. Either or both contributed to multiple organ failure.

• Secondary issues: Effects of severe dehydration and debilitation. Dehydration resulted from the immediate distress that led to the ER visit. Debilitation reflected the nine year long illnesses of GCA and PMR and the use of prednisone and other medications needed to sustain reasonable health.

A timeline of the traumatic events that took place at home and at the hospital ER are provided in the following table. Authoritative medical literature that describes the urgent need for corticosteroid therapy in critical ill patients who are on daily prednisone follows the table.

Timeline of Pearl's trauma and sedation events at home and in the hospital ER
Date & Time	Who	Event
10/17/2007
8:00 PM	Pearl	Started vomiting, diarrhea and stomach pain
10/18/2007
2:30 AM	James	Severe chills set in, dehydrated, very weak - called paramedics for hospital transport
3:15 AM	Paramedics	Sedated with 2 intranasal bolus doses of Versed (5 mg), administered oxygen via tubing
4:00 AM	Paramedics	Presented Pearl for admittance to ER and advised ER they administered Versed
5:25 AM	ER	Blood test; continued oxygen via tubing (nasal cannula)
7:19 AM	ER	Time seen by ER physician - as recorded on Hospital Emergency Physician Record
8:38 AM	ER	Started Zofran, 4 mg by IVP (IV push)
8:40 AM	ER	Started Dilaudid, .5 mg by IVP
9:00 AM	ER	Started Cipro, 400 mg/250 mls by IVPB (IV piggyback)
9:00 AM	ER	Urinalysis - Clear, normal and favorable negative readings
9:30 AM	ER	CT Scan of abdomen; organs including pancreas are normal except spleen and kidneys are atrophic; no aortic aneurysm, intestinal perforations or internal bleeding are evident
11:08 AM	Radiologist	X-ray of chest, no problems noted
11:30 AM	Radiologist	X-ray of abdomen, no problems noted
1:50 PM	ER	Flagyl, 500 mg by PO (oral)
2:45 PM	ER	Offered two hydrocodone pills (strength not listed); Pearl took only one
2:48 PM	ER	Oxygen delivery changed from tubing to face mask
4:15 PM	James	ER doctor advised me that he prescribed stress dose of hydrocortisone - 100 mg every
		8 hrs by IV. No ER record that I was given shows that hydrocortisone was ever actually administered other than pulmonologist’s report at 5:43 pm stating it happened.
4:40 PM	Dr.'s report	Septic shock noted by ER doctor in Final Report dictated at this time
4:50 PM	ER	Levophed drip, 4 mg/250 ml by IV; 40 mcg/min; preparatory for intubation
4:57 PM	ER	Levophed drip, 30 mcg/min; preparatory for intubation
5:10 PM	ER	Etomidate, 10 mg by IV; preparatory for intubation
5:10 PM	ER	Versed, 4 mg by IV; preparatory for intubation
5:12 PM	ER nurse	Endotracheal intubation reported by nurse on duty
5:36 PM	ER	Lactate elevated @ 6.14 (should be < 1.25) in arterial blood test
5:36 PM	ER	Started ventilator to replace oxygen
5:43 PM	Pulmonologist	Endotracheal intubation reported by pulmonologist consultant
5:44 PM	Pulmonologist	Shock noted and central line catheter placed in femoral vein
5:55 PM	ER	Versed drip, 0.5 mcg/min (IV)
6:00 PM	ER	Versed drip, 10 mcg/min
6:18 PM	ER nurse	Unable to measure blood pressure in arms or legs; pulses very weak - shock?
6:25 PM	Radiologist	X-ray of chest, no lung problems but found endotracheal tube is too deep, notified EAC
6:28 PM	ER	Sodium Bicarb drip by IV; 80 ml/hr
6:28 PM	ER	Normal saline, 120 ml/hr (IV)
6:30 PM	ER	Amylase total is 546 (normal is <125); Lipase is normal at 44 in blood chemistry test
6:47 PM	ER	Versed drip, 0.5 mcg/min
7:00 PM	ER nurse	Blood pressure and heart rate back at typical readings in this report
7:26 PM	Nephrologist	Prescribed Xigris according to his report at this time; indicated it was given in two reports
8:01 PM	ER nurse	Discharged from ER, sent to ICU
9:00 PM	Dr.'s report	Rt leg wound drainage smear and culture - no organisms or growth in 3 days
10/19/2007
6:26 AM	Radiologist	X-ray of chest, endotracheal tube not corrected; progressing right side infiltrates
10:20 AM	ICU	Pearl expired

Authoritative medical reference supporting the need for corticosteroid replacement therapy in critically ill patients with established hypoadrenalism

N Engl J Med. 2003 Feb 20;348(8):727-34. (Ref: 129.)????PMID: 12594318

Corticosteroid insufficiency in acutely ill patients. Cooper MS, Stewart PM. Division of Medical Sciences, University of Birmingham, Queen Elizabeth Hospital, Edgbaston, Birmingham, United Kingdom.

Ref: Page 731. "Critically ill patients with established hypoadrenalism … should be treated with intravenous or intramuscular hydrocortisone at a dose of 50 mg every six hours."

Ref: Page 733. "Patients receiving corticosteroid-replacement therapy should be advised to double the daily dose during febrile illnesses, after accidents, or when they have mental stress caused by such events as an important academic examination. If the patient is vomiting, parenteral hydrocortisone must be given urgently, as mentioned above. ……. Patients receiving corticosteroid therapy should register for a Medic Alert bracelet or necklace and carry a medical identification card, stating the need for corticosteroid replacement."

Pearl had a medical identification card which stated her emergency need for 12 mg daily of prednisone. The card was shown to hospital ER staff on the morning of admittance but it didn’t achieve the intended purpose despite my pleading for prednisone supplementation at that time.

Refer to Appendix 11 for details regarding drug interactions for the medications Pearl was taking. Also find information about methotrexate and pancreatitis, and contraindications for administration to Pearl regarding Versed, Dilaudid, hydrocodone, Levophed and Etomidate.

 

 

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