The Real Impact of E. coli Tainted Romaine Lettuce from Yuma

I was reading on Food Safety News, “Yuma romaine growers hopeful harvest will end without E. coli issues” https://www.foodsafetynews.com/2019/03/yuma-romaine-growers-hopeful-harvest-will-end-without-e-coli-issues/ and could not help but think that what was missing was a story of a customer.  Here one is:

Jordan Anglen is a 24-year-old young man residing in Meridian, Idaho with his girlfriend Josie. Jordan was among those who became severely ill after consuming E. colicontaminated romaine lettuce. On March 25, 2018, Jordan purchased and ate a Chicken Caesar Salad containing E. coli-contaminated romaine lettuce at the Costco Food Court at 2051 S. Cole Rd., Boise, Idaho.

Jordan Anglen before his illness

Primary Health Medical Group

On March 29, 2018, Jordan presented to Primary Health Medical Group, where Shannon Bordes, FNP evaluated him for a chief complaint of “diarrhea, back pain, body achy,” which he stated had begun the night before. Jordan described a two-day history of symptoms, which had also included joint pain, lightheadedness, lack of appetite, lower back pain, fever, and chills. He stated he had taken ibuprofen the previous afternoon at 5:30 PM for his symptoms. He was currently tolerating oral fluids and had been able to eat a small amount of food that morning. He had not been vomiting but was intermittently nauseated. On exam, NP Bordes found Jordan afebrile with a mostly unremarkable exam, which was significant mainly for a rapid heartbeat of 100 and a marginally elevated blood pressure of 137/81. He was mildly febrile with a temperature of 99.3ºF.[1]

NP Bordes thought Jordan’s clinical presentation was most consistent with viral gastroenteritis, which seemed to be already improving. She approved the use of Imodium to slow down his diarrhea, advising him to follow a clear liquid diet, and increase his intake slowly with electrolyte-containing fluids. Once his diarrhea was resolved, she told him he could advance his diet to more solid foods. If he had worsening symptoms, such as increasing fevers or abdominal pain, or bloody or dark stools, she advised him to return immediately or go to the ER. Jordan went home and tried to follow the instructions given him by the nurse practitioner, but he only got worse and worse.

St. Luke’s Meridian Medical Center

On March 30, 2018 at 2:45 AM, Jordan presented to St. Luke’s Meridian Medical Center, where Konrad Kessler, MD evaluated him in the emergency department for his worsening abdominal pain, nausea, vomiting, and diarrhea. After vomiting for hours without any intake, Jordan was now experiencing retching and dry heaves, which felt much worse to him than if he had something to throw up. He told the doctor about the clinic visit where he was diagnosed with a virus, but since then he began experiencing abdominal pain “before, after and during” bowel movements. His stool had also turned bloody for the three hours preceding his coming to the ER. Currently, Jordan rated his pain as 10/10 in severity, with was non-radiating and did not get better or worse with anything he tried. He was still urinating normally, as far as he could tell.

On exam, Dr. Kessler found Jordan dehydrated with tacky mucous membranes, and dry and cracked lips. His vital signs were in normal range, and his lungs were clear. Jordan’s abdomen was diffusely tender to even light palpation, and it was especially severe in his left side with rebound tenderness, and tenderness to percussion. His right abdomen was also tender, but less so.

Among the disorders Dr. Kessler thought might be causing Jordan’s symptoms, he considered toxic megacolon,^[2]colitis, gastroenteritis, bowel obstruction, among others. He planned to obtain diagnostic laboratory studies and imaging while they attempted to treat him symptomatically with pain and nausea medications. He started Jordan on intravenous fluids and sent blood, urine, and stool to the lab for analysis.

The lab soon reported a number of abnormalities, including an elevated white blood cell count of 14.59, which contained a predominance of neutrophils.[3] He also had a slightly elevated hemoglobin of 18.1, reflecting his severe dehydration. His kidney function was currently in normal range, with a BUN and creatinine of 18 and 0.91, and his liver function was similarly normal.[4]His lipase was in normal range. His serum electrolytes were slightly abnormal, with his bicarbonate just out of normal range.

At 3:18 AM, radiologist Brian McMahan, MD performed an IV-contrast-enhanced CT of Jordan’s abdomen and pelvis, during which he found no signs of obstruction. Jordan’s appendix was surgically absent, an expected finding as he had it removed in 2013. Dr. McMahan observed thickening of the descending and transverse colon, “likely due to underdistention.” The ascending colon was also inflamed, and there was a trace of free fluid surrounding it. Dr. McMahan thought Jordan’s CT was consistent with mild colitis, although the changes he saw were largely nonspecific.

Dr. McMahan kept Jordan under observation in the ER for an hour and a half, after which he reported that his symptoms were much improved. He declined any pain or nausea medications, feeling that the reversal of his dehydration with IV fluids was helping him enough. The doctor discussed the diagnostic findings from Jordan’s labs and CT scan with him and his mother, and he reassured them that he appeared to have a gastrointestinal illness that should be self-limited. Dr. McMahan deemed Jordan safe for outpatient management and discharged him home from the ER with a prescription for Zofran in case he needed it. He encouraged him to stay as well hydrated as possible and to return if he noticed any blood in his emesis, or he had persistent vomiting, dehydration, or uncontrolled abdominal pain. Jordan left the ER at around 4:30 AM.

Getting worse at home…

Unfortunately, Jordan went home and grew steadily worse. After his initial improvement with IV hydration in the ER, he was unable to keep up with oral fluids, and his diarrhea increased in frequency. Even worse was the rectal bleeding—Jordan’s bloody diarrhea began to contain less stool and more blood, and by 11 PM on the 30^th, it appeared to be only bright red blood. His lightheadedness returned, and he began feeling very dizzy, which alarmed his family.

St. Luke’s Meridian Medical Center – ER – sent home again

On Saturday, March 31, 2018 at 1:02 AM, Jordan returned to the Meridian ER, where Steven N. Wyman, MD evaluated him and sent repeat blood work to the lab. Jordan’s white blood cell count had increased to 22.76 and his platelets began to fall, now measuring 138K. A stool test for toxigenic C. difficilewas negative. Dr. Wyman restarted Jordan on IV fluids and gave him a dose of IV antibiotics (ciprofloxacin). At 3 AM sent Jordan home with a prescription to take oral ciprofloxacin 500 mg twice daily for a week and to see gastroenterologist Mark Mallory, MD on Monday if his symptoms persisted.

Confirmation of Shiga toxinin stool

At 4 AM, the hospital laboratory reported at critical value to the ER that Jordan’s stool had returned positive results for Shiga toxin. Dr. Wyman called Jordan at home and was told that he was still having bloody diarrhea. “I requested that he return to the Emergency Department for reevaluation.”

Return to Meridian ER diagnosed with STEC infection – antibiotics stopped

Jordan arrived back at the ER at 8 PM on April 1, 2018. Dr. Wyman was on duty when he arrived, and he told the doctor that he continued to have bloody diarrhea every 5-30 minutes. Dr. Wyman ordered intravenous fluids and reassessment of his blood work. The lab soon returned results showing an elevated white count of 28.83, and low platelets of 60K. His BUN and creatinine were 25 and 1.32. Dr. Wyman commented that Jordan had now developed “some minor renal insufficiency with a creatinine of 1.32 and thrombocytopenia with a platelet count of 60,000. Bilirubin is also elevated at 4.4.” His transaminases were in normal range. Dr. Wyman again consulted with gastroenterology and the consensus was to discontinue all antibiotics and admit Jordan for supportive care. Jordan’s diagnoses upon leaving the ER were: “Shiga toxin-producing Escherichia coliinfection” (STEC), “Renal insufficiency,” and “Thrombocytopenia.”

Admission under contact isolation – Meridian Hospital Day 1

On April 1, 2018 at 10:41 PM, hospitalist Mary Ann Huntington, MD formally admitted Jordan to the hospital as an inpatient under contact isolation, diagnosing him with “sepsis,” “STEC,” and “AKI.” Dr. Huntington reviewed Jordan’s history of his present bloody diarrhea, which had now been going on for four days, including his two ER visits and now return to the hospital for admission. He continued to complain of diffuse crampy abdominal pain, some nausea, but no current vomiting. Despite not having eaten for four days, he stated he was not hungry. Dr. Huntington noted that the antibiotics that were started had since been discontinued with this admit, since his stool studies returned positive results for Shiga toxin. She addressed his diagnosis of “sepsis,” commenting that it was related to the Shiga toxin producing E. coli— “Shigella, Salmonella, Campylobacterwere negative. C. difficilewas negative.” Dr. Huntington thought Jordan’s acute kidney injury was likely secondary to volume depletion from recurrent diarrhea; however, she thought it was possible that Jordan was developing hemolytic uremic syndrome.

Meridian Hospital Day 2-3 – evolving HUS, oliguria

Hospitalist Meaghen Friel, MD came in to see Jordan during morning rounds on April 2, 2018. He continued to have bloody diarrhea, and his exam was significant for “profound rebound pain.” She checked his morning labs, which showed an improved WBC of 23.57, but a worsening of his acute kidney injury (BUN 32, creatinine 1.42). She noted that he had not had any urinary output in the prior 24 hours. His platelets had dropped to 26K, which increased her concern for HUS, so she ordered an LDH and haptoglobin.[5]

On April 3, 2018, at 1:43 PM, Aaron A. Fearday, MD came in for a nephrology consultation to evaluate Jordan’s acute kidney injury, reviewing his worsening renal function labs. Jordan reported that he was in his usual state of good health until 6 days before, at which time he developed abdominal pain and diarrhea so severe, it caused him to seek care twice in the ER. Jordan stated that he was initially taking Imodium for the diarrhea. Dr. Fearday noted that Jordan’s father was concerned about his son’s nutrition, but Jordan had declined a feeding tube. Dr. Fearday discussed with Jordan and his dad in detail that parenteral nutrition was not a good idea at that time. He agreed with Jordan’s other providers that he had HUS. Dr. Fearday commented in his chart note:

The patient’s labs are all consistent [with] thrombotic microangiopathy given his hemolysis, thrombocytopenia, and acute kidney injury. In the setting of diffused diarrhea and stool culture, Williams will also be seeing the patient later today. His father was concerned that we were ‘not doing anything.’ I explained that we are giving him fluids and we are also closely watching his clinical status. I reiterated that antibiotics and anti-motility agents can often prolong the infection and the symptoms and are not recommended at this time.

Dr. Fearday also discussed with Jordan and his dad that it was going to “… take time for his body to fight this infection. I explained that if the kidney function worsens, we could do dialysis, but I don’t think that there is an indication at this time.” His father wanted to know if they could do dialysis to “ease the burden on the kidney,” and Dr. Fearday explained that dialysis would not achieve that goal: “I explained that dialysis cleans the blood when the kidneys are not working. His mother and father are very anxious about the illness of Jordan. I explained that we are watching his clinical course closely.”

Hematology consultation – platelet transfusion

Travis Williams DO came in for a hematology consultation when it became clear that Jordan was developing hemolytic uremic syndrome. His BUN and creatinine were now 57 and 3.22, and his platelets dropped further to just 13K. His LDH was elevated at 2705. He noted that Jordan was given IV ciprofloxacin in the ER and since taken two days of the oral medication before it was stopped at the beginning of this admit. Jordan stated that he was actually feeling better, although he was having difficulty urinating.

Dr. Williams concurred with Jordan’s diagnoses of  “Shiga Toxin E. coliwith HUS (STEC-HUS) with progressive thrombocytopenia, renal failure, hyperbilirubinemia, elevated LDH.” He noted that Jordan was still having bloody stools, but no fevers, altered mental status or confusion. He saw no current indication for total plasma exchange (TPE) or fresh frozen plasma (FFP) infusions; however, since Jordan was significantly thrombocytopenic, he recommended a platelet transfusion to keep his counts above 20K while currently bleeding.

Jordan received a platelet transfusion that afternoon. Dr. Williams ordered a transfusion of packed red blood cells (pRBCs) if Jordan’s hemoglobin fell below 8 g/dL, and he wanted some other labs checked, commenting: “To be complete I would ensure coags, fibrinogen, and ADAMTS13^[6]have been checked. Typically, HUS is more platelet consumptive as opposed to coagulation factors consumption.” Meanwhile, he advised supportive measures with intravenous hydration and continued renal support by nephrology.

Meridian Hospital Day 4 – continued oliguria

On April 4, 2018, hospitalist Shanna Case, MD evaluated Jordan during morning rounds. He complained of continued incessant bloody diarrhea, describing some 30 episodes during the prior 24 hours, which actually represented a decrease in number. His pain was under control, but he required frequent dosing of narcotic pain medications (Dilaudid). He was unable to tolerate anything orally except for a small amount of water. Jordan was barely producing any urine and was effectively anuric. His mental status appeared intact and he denied confusion, about which his mother agreed.

Jordan was visited by hematology and nephrology. Jordan reported frequent bowel movements that still contained some blood. Dr. Fearday noted that his renal function had worsened overnight (BUN 79, creatinine 4.79). Jordan thought he was producing some urine, but the doctor observed that it was actually very little. He explained that they would assess him daily for the need for dialysis. “There is a chance he may benefit from dialysis in the next day or two if there is no clinical improvement.” Jordan was becoming volume overloaded, and he was hyponatremic as well as oliguric. Dr. Fearday recommended they stop his IV fluids the next day if that did not change. Jordan’s mother was present at his bedside discussed the care plan.

Meridian Hospital Day 5 – marginal urine increase

On April 5, 2018, Dr. Case reviewed Jordan’s morning labs, which continued to reflect sepsis, hemolytic anemia, thrombocytopenia, and worsening renal function, as well as marginal liver dysfunction (WBC 39.94, hemoglobin 9.2, hematocrit 26.1, platelets 21K, BUN 94, creatinine 5.42, AST 61). While his leukocytosis was worse, his tachycardia had improved, and his serum lactate normalized. His diarrhea was also improving, although still frequent, and his stools less bloody. Dr. Case commented that Jordan’s HUS was reported to the Department of Health on the 5^thby nephrology. She noted his platelets were stable overnight, and his hemoglobin was just high enough to avoid a blood transfusion. She commented that nephrology was following his renal function, which continued to worsen secondary to the toxic effect of Shiga toxin Escherichia coli. Improving urine output. Jordan’s urinary output increased somewhat, and she saw no current indication for hemodialysis at that time. He was still hyponatremic and hypervolemic and remained on reduced fluids per nephrology recommendations to address those things.

At 10 PM, Sandra Van Hooser, RN summoned the hospitalist when Jordan began complaining of crushing chest pain to the left side of his chest. The pain did not radiate or get worse with deep inspirations and Jordan did not require supplemental oxygen. He continued to make frequent trips to the bathroom for diarrhea. He had not been measuring his urine output, stating it was too difficult with the diarrhea. Jordan had been suffering with hiccups all day, which was thought to have something to do with the chest pain episode, and the physician did not think he needed to be placed on cardiac monitoring with an EKG.

Meridian Hospital Day 6-7 – blood transfusion pRBCs – improving urinary output

On April 6, 2018, Robert Davidson, MD came in for nephrology, finding Jordan much the same as the day before, including the unrelenting hiccups. He made no changes to his diagnoses or care plan.

Dr. Case came in a little later and evaluated Jordan, who told her that his diarrhea had become bloody again overnight and his abdominal pain was not well controlled, even on the narcotics being given “as needed.” He was feeling very fatigued and lightheaded that day with ambulation. His morning labs showed a WBC 41.57, hemoglobin 7.4, hematocrit 21.1, platelets 24K, BUN 93, creatinine 4.44, and LDH 2776. Dr. Case ordered a blood transfusion of two units pRBC’s (packed red blood cells). She made some adjustments to Jordan’s narcotic pain medication orders, hoping to get his pain under better control. Jordan’s urine output was improving slightly that day.

At 5:47 PM, Dr. Williams came in for hematology/oncology and went over Jordan’s lab results. His mother was at the bedside, and the doctor explained that his extremely elevated white blood cell count was reflective of ongoing bone marrow issues related to hemolytic uremic syndrome, with its associated hemolytic anemic and thrombocytopenia. He observed that Jordan’s elevated LDH and serum ferritin were consistent with hemolysis from Shiga toxin. If Jordan developed fevers, then he would be more concerned and would order blood cultures to rule out a systemic infection. He explained that antibiotics were contraindicated with HUS because they could actually make his condition worse.

Dr. Case came in to see Jordan on April 7, 2018, observing that his urinary output was improving daily. His diarrhea was no longer bloody, and the frequency was down to hourly. He was able to tolerate small amounts of fruit and juice. He stated his pain was better controlled. His lab improved that morning since yesterday’s blood transfusion (WBC 37.07, hemoglobin 8.1, hematocrit 23.0, platelets 28K, BUN 83, creatinine 3.46, AST 215, ALT 56, total bili 3.1, LDH 3168).

Dr. Davidson came in for nephrology, and Jordan expressed a desire to go home. He stated his diarrhea had improved and he was urinating more, hoping that would convince the doctor. Dr. Davidson did not think Jordan’s HUS was getting worse at this point, but his LDH was still very high and probably reflected ongoing hemolysis. He explained to Jordan and his mom that he was too ill to be discharged any time soon.

Meridian Hospital Day 8 – development of neurologic symptoms (myoclonus)

When Dr. Case evaluated Jordan around 8 AM on April 8, 2018, she was happy to see that he was having even less frequent diarrhea (every 2 hours) that continued to be nonbloody, but he still had a very poor appetite and was taking in only a little fruit and juice. He appeared exhausted, and he stated he was not sleeping much. His labs were still markedly abnormal, albeit improving (WBC 31.00, hemoglobin 7.3, hematocrit 21.6, platelets 41K, BUN 69, creatinine 2.65, LDH 2556).

Of greater concern was that Jordan had developed a new neurologic symptom, exhibiting episodes of jerking when he drifted off to sleep. In addition, he had two episodes of nosebleeds overnight; however, his coagulation panel was reassuring. He was still afebrile and denied any confusion or other mental status changes. Dr. Case conferred with neurology, who thought the jerking episodes were probably myoclonus from uremia, although Jordan’s BUN was gradually improving.

Neurology Consultation

At 1:12 PM, neurologist Daniel Abenroth, MD came in to evaluate Jordan. Upon reviewing the history of his symptoms and talking to Jordan and his mom, he learned that he had been having the jerking movements for 2-3 days. Dr. Abenroth did a neuro assessment commented in his chart note:

23-year male who has developed acute myoclonus in the setting of hemolytic uremic syndrome. Uremia itself is a known cause of myoclonus. Though he is producing urine, he’s been clearly dealing with acute kidney injury and HUS, which has also resulted in a number of metabolic abnormalities. His acute myoclonus is likely the result of his HUS, AKI, and metabolic disturbances. My concern for underlying seizures or other causes of myoclonus is low at this time. This myoclonus is typically a self-limited phenomenon that improves as the renal and metabolic disturbances improve. This is unlikely to represent the onset of new chronic condition. Typical symptomatic treatment modalities include Keppra[7]and [benzodiazepines]. Treatment for the myoclonus in his case is not essential (his myoclonus is relatively rare during the day; 3-4 reported episodes today), though treatment could provide symptomatic relief. This was explained to the patient. At this time, he prefers to defer more meds unless his condition fails to improve or worsens.

Seizures – Rapid Response Team (RRT) response

The St. Luke’s Internal Medicine (SLIM) service paged Dr. Abenroth around 8:45 PM in the evening on April 8, 2018, after Jordan had an episode of reported arm twitching while on the toilet. The staff found Jordan on the bathroom floor with twitching arms and legs. Afterward, he appeared to be agitated. The nursing staff and family felt this episode was different and looked more like a seizure instead of myoclonus.

The Rapid Response Team documented Jordan’s seizure episode:

STAFF NURSE FOR UNIT.

Ryan Fox, RN 8:05 PM. I heard a call for “help” from the pt’s room. I was preparing to gown-up where I observed the pt seated on the toilet with his legs extended and leaning his torso and head back while his shoulders and head were being supported by his significant other. The pt appeared to be seizing at that time. I immediately entered the room and took over for the pt’s [significant other] in protecting his head. The pt was having what appeared to be a tonic clonic seizure; his legs and arms were fully extended and the pt was convulsing. The pt had bloody frothy saliva coming from his mouth. Kelly Wolfe, RN, entered the room and I requested that she call a rapid response and get staff assistance.

The seizure lasted approximately 28 seconds from the time I entered the room. I instructed the family to lay down some blankets and a pillow on the ground next to the toilet and the pt was transferred from the toilet to the ground. The pt appeared to be in a post-ictal state after being positioned on the ground; the pt was non-verbal, inactive, and had a distant gaze in his eyes with nystagmus that would not focus on me. Vital signs were obtained and were found to be stable.

CRISIS RN – RAPID RESPONSE TEAM

Lisa Stimpson, RN 8:30 PM. Rapid response called for this patient who had seizure-like activity while on the toilet. Event witnessed by staff and family. Arrived to find patient awake and lying on bathroom floor. Pt had been placed on oxygen and carefully assisted to floor for safety w/o fall or injury except for small bite to lower lip with scant bleeding. Pt appears to be postictal. Not able to maintain eye contact or follow commands, incomprehensible speech, moving all extremities spontaneously. GCS 11. PERRL. Placed green sheet under pt and used lift to return to bed. Seizure pads placed on bed. Family at bedside, however pt remains altered, agitated and tachycardic. Hospitalist came promptly to bedside to assess. Orders for Keppra and brain MRI scheduled for morning. BG 167. Pt now calm. Still not speaking to family but maintaining eye contact. HR trending down to baseline. Keppra infusing.

SLIM EVENT NOTE 8:33 PM

Daniel Orchard, MD. My colleague Sam Gallo PA was paged that the patient may have had a seizure. In brief Jordan Anglen is a 23 yo man here with E. Coli causing HUS, AKI, thrombocytopenia and anemia. He developed myoclonic jerks as a result of the uremia and was evaluated by neurologist. Dr. Abenroth earlier today. The patient chose to defer meds at that time. A full workup for seizure including MRI/EEG was not recommended given the natural course of myoclonic jerks and the likelihood of seizure was low.

When I arrive at the room, the patient’s girlfriend, mother, and father are gowning up to go in and tell me that I’m needed right away because he is having a seizure. The girlfriend tells me he was on the toilet when he started to have jerking movements like earlier today, he also reached out suddenly with both arms grabbing the toilet. There was no head trauma, but he was not responding to questions. On exam, his eyes are not dilated, he is moving all extremities spontaneously, he is purposefully moving his hands in front of his face and seems to be looking at them, he sometimes groans/moans. He had no evidence of head trauma. He doesn’t seem sluggish as is typically found during a post-ictal state. He is tachycardic.

Dr. Abenroth diagnosed Jordan with “probable acute seizure” and started him on Keppra 500 mg twice daily (renal dosing for seizure) and ordered an MRI for the following day. He deferred an EEG for now, commenting, “Whether myoclonus or seizures, we will treat with Keppra. Furthermore, whether myoclonus or seizure, either is likely due to his HUS and several metabolic disturbances. This is unlikely to represent the new onset of a chronic seizure disorder.” If needed for breakthrough seizures, Dr. Abenroth ordered Ativan 1-2 mg intravenously. He planned to see Jordan for a reassessment in the morning.

Jordan not improving after seizure – incontinent of bowel and bladder

After Jordan’s seizure, his family was understandably extremely upset and worried about their son. They soon summoned the nursing staff that Jordan seemed to be getting much worse. At 10:30 PM, Lisa Stimpson, RN called the SLIM service to communicate her concern that, 2.5 hours after the seizure, Jordan remained non-communicative and unable to maintain eye contact or follow commands, and he was now incontinent of bowel and bladder. He would moan rather than speak his answers.

The nurse spoke with both Sam Gallo, PA and Daniel Orchard, MD. The family requested that an MRI be done immediately and not wait for morning. She conveyed a message to the doctors: “Family is very concerned and dissatisfied.” Despite the family’s request, the doctors were not convinced of the need to return to the unit—both felt it appropriate to continue with observation and proceeding with the MRI in the morning as ordered.

Meridian Hospital Day 9 – more seizure activity, incontinence

Shortly after midnight on April 9, 2018, the nursing staff urgently paged hospitalist Mousumi Nandy, MD for another “event” that was still ongoing. Jordan’s mental status appeared to be worsening, with three additional episodes of incontinence of bowel and bladder. His parents were at the bedside and extremely anxious and upset and demanded that Jordan to be seen by a doctor.

Dr. Nandy soon arrived on the unit and spoke with Jordan’s nurse and his family, who told him that Jordan had an observed 28-seconds-long generalized tonic-clonic seizure, in the presence of nursing staff, and following that he was not following any commands, which was a definite change from the time of his first seizure. Prior to the seizure, “… patient was alert awake doing fine.” “Family both parents are very concerned. Mom is wanting to get something done now to find answers regarding his changes.”

Dr. Nandy observed that Jordan was awake but not responding to any verbal or tactile commands. His pupils were reactive and equal. He was unable to cooperate for a neurological exam; however, he moved all four extremities on his own. During Dr. Nandy’s first examination, he observed some “posturing” with Jordan’s right elbow flexed and his hand curled inside, as well as the left hand straight but fist curled inside towards the body. He continued to moan intermittently. During Dr. Nandy’s second examination, Jordan did not exhibit posturing but “… was flinging his hands in the air and then held it over his forehead, resting to move.”

Moved to ICU for seizure watch

Dr. Nandy ordered Jordan moved to the ICU to for seizure monitoring, and he wanted a stat CT of his head to rule out a bleed. He ordered stat labs to include a complete blood count, metabolic panel, and LDH. At 2:32 AM, radiologist John Waltz, MD performed an unenhanced CT of Jordan’s head, which he read as normal.

Dr. Nandy paged neurologist Dr. Abenroth to inform him that he had moved Jordan to the ICU. He explained that Jordan had been persistently encephalopathic since the seizure at 8 PM a few hours earlier, with reported episodes of flexion of his arms (predominantly one arm). He stated that Jordan had remained non-communicative and was receiving renal dosing of Keppra through his IV. “This remains as a significant neurologic change as compared to when I last saw him [yesterday] afternoon, when he was neurologically normal.”

TTP versus HUS – recommendation for plasmapheresis[8]

Dr. Nandy remained concerned for the possibility of TTP^[9]as the cause of Jordan’s neurologic change. Dr. Abenroth addressed this possibility but deferred to hematology and the SLIM team:

TTP can certainly cause a variety of neurologic symptoms, including seizure, encephalopathy, or stroke. Similar changes can also be found in HUS, though significant acute neurologic change remains one of the hallmarks of TTP. The diagnosis of TIP, especially as it relates to the subtle differences between TTP and HUS is beyond the expertise of neurology. As such, I defer ultimate diagnosis of TTP vs. HUS to experts of that disease. However, Neurology recognizes the importance of prompt treatment for TTP with plasmapheresis in cases of suspected disease. As such, if the SLIM and Hematology services have a significantly high suspicion of TTP, then Neurology recommends treatment with plasmapheresis. Plasmapheresis has also been used in cases of atypical HUS. If the SLIM and hematology services feel that patient has atypical HUS, plasmapheresis is also a consideration. Ultimately, the diagnosis of TTP (and whether plasmapheresis is ultimately used) will be deferred to the experts of that condition (hematology and SLIM).

Dr. Abenroth pointed out that a stat head CT was read as normal. He thought it unlikely that Jordan was suffering a stroke, commenting: “In the chance it is stroke, no typical acute stroke treatment is recommended (tPA and aspirin are contraindicated on account of thrombocytopenia) …” In the setting of Jordan’s recent seizure, Dr. Abenroth thought his current condition might simply be post-ictal, but an ongoing seizure was also possible. He recommended that SLIM give Jordan another 2 mg of Ativan now to assess for neurologic change. If he continued to have persistent neurologic symptoms despite the dosing of benzodiazepines, along with additional time to recover from a possible post-ictal state, then Dr. Abenroth recommended that Jordan be transferred to Boise early in the morning (about 8 AM) so that continuous EEG monitoring could be initiated immediately.

After speaking with Dr. Abenroth, Dr. Nandy discussed Jordan’s clinical presentation with the hematologist on call, Dr. Alluri. He expressed his concerns about Jordan’s sudden change of mental status in a patient with HUS and whether he needed to be started on plasmapheresis. “At this point her recommendation was to continue to watch him, since his labs are improving, she will talk to Dr. Williams from hematology who had seen the patient earlier to follow up and decide whether patient would benefit from plasmapheresis or watchful waiting.”

Jordan’s parents were present for the consultations, and Dr. Nandy talked with them at length about their son’s care plan. He ordered the placement of a Foley catheter at 4:39 AM to deal with Jordan’s continued incontinence.

In ICU and not improving – tachycardic and febrile to 101.7ºF

At 8 AM on April 9, 2018, Shanna Case, MD and nephrologist Robert Davidson, MD came in to evaluate Jordan in the ICU, noting that he had been transferred there during the night because of seizure activity. The nursing staff indicated that he had been febrile that morning. His morning labs were in and continued to reflect sepsis, renal dysfunction associated with HUS, and some degree of liver dysfunction (WBC 30.55, hemoglobin 8.8, hematocrit 25.1, platelets 62, BUN 62, creatinine 2.26, AST 132, ALT 79, LDH 2405). Jordan was tachycardic with heart rates ranging from 117-128, with at least one oxygen desaturation down to 88%. The doctors reassessed Jordan’s differential diagnoses, which now included “HUS-TTP versus status epilepticus[10]versus less likely stroke.” They continued his seizure treatment with Keppra, adding Vimpat[11]pending implementation of continuous EEG monitoring.

Neurology consulting recommended a trial of plasmapheresis “… due to clinical decline per discussions with hematology, nephrology.” Upon review of Jordan’s labs, the doctors noted that that his ADAMST13 had come back normal and his complement levels were low, making atypical HUS unlikely. His renal function, while still significantly impaired, was improving steadily and he continued to produce greater amounts of urine. He was currently running a fever of 101.7ºF, but the doctors continued to avoid giving him any antibiotics. They continued his narcotic pain medications and anti-emetics.

Transfer to St. Luke’s Boise for cEEG and plasmapheresis

Travis Williams, DO came in for hematology at 8:14 AM, noting Jordan’s seizure activity, high fevers, and confusion. Given Jordan’s increasingly critical status and move to the ICU, his care team was of the consensus that he should be transferred to Boise for a higher level of care, where he could receive continuous EEG monitoring and be started on plasmapheresis, although Jordan was considered to have typical D+HUS and not atypical HUS.^[12]Rather, Dr. Williams’ recommendation to start plasmapheresis was based on Jordan’s change in mental status, which he felt was directly related to Shiga toxins. “Schistocytes seen on peripheral smear. Elevated LDH and a ferritin consistent with hemolysis from Shiga toxin.” He discussed this with nephrologist Dr. Davidson, who concurred, and they contacted the critical care team in Boise with a plan to begin plasmapheresis as soon as he got there.

Jordan looking gaunt and wobbly with a walker…

Boise Hospital Day 15-19 – preparing for discharge to rehab

On Sunday, April 15, 2018, Dr. Madison came in for the hospitalist service and continued transitioning Jordan to oral medications, which included Keppra and Vimpat, the latter of which was about to be discontinued in two days. He was advanced to a regular diet. Natasha Pappas came in for case management to discuss with Jordan and his mom his discharge to rehab, which could occur as soon as the next day. They discussed preferred rehab facilities, settling on St. Luke’s Rehab as their first choice. If Jordan had his way, he would just head home in his seriously deconditioned state, but his mom and the therapists convinced him of the utility of building his strength and stamina before doing that. His mom wanted to make sure that, wherever Jordan went, they could monitor his blood in case he needed more transfusions.

Dr. Madison resumed discharge discussions with Jordan and his parents the next day, and his dad was concerned about how somnolent the anti-seizure medications made him. However, he understood the important of seizure prevention at least for the time being. Jordan still exhibited generalized weakness, but he was ambulating the halls and working hard at PT and OT.

On April 17, 2018, Dr. Madison observed that Jordan was very drowsy, which he attributed to a recent Keppra dose. He continued to be weak and unsteady on his feet, but he was not having any seizures. His labs continued to exhibit improvement (WBC 8.08, hemoglobin 8.2, hematocrit 25.0, platelets 238K, BUN 28, creatinine 0.98) and his blood cultures had not grown any bacteria. He was eating and drinking without difficulty, and he was having normal urinary output and bowel movements.

Jordan was growing very bored and wanted to get out of the hospital. He worked daily with PT, OT, and SLP, the latter of which was focusing on memory strategies, attention tasks, and safety awareness, among other cognitive issues that had suffered from his long critical illness. By the 19^th, Jordan was progressing towards his self-care goals, although he was still limited by decreased insight and occasional safety awareness. He exhibited occasional impulsiveness but was able to self-correct without cues (“this may be pt’s baseline due to being young and active”). He was able to perform grooming at the sink with close supervision. His swallow function was near baseline, and SLP was able to discontinue therapy at that time. PT worked with him on higher balance exercises and cognition for safe transition to home.

Boise Hospital Day 20 – getting ready to leave for rehab

On April 20, 2018, hospitalist Allyson Komori, DO evaluated Jordan for discharge from the hospital to sub-acute inpatient rehabilitation. She thought he was ready for transfer to St. Luke’s Rehabilitation Hospital, where they would continue working with him on ongoing strengthening and improvement in his stamina for a safe transition to home. Dr. Komori discharged Jordan from the hospital with the following diagnoses:

Principle Final Discharge Diagnosis:

1. STEC (Shiga toxin-producing Escherichia coli) infection

Secondary Discharge Diagnoses:

1. Hemolytic uremic syndrome
2. Seizure disorder with myoclonus
3. Acute renal injury
4. Metabolic encephalopathy
5. Dysphagia
6. Protein calorie malnutrition
7. Hemolytic anemia
8. Thrombocytopenia
9. Hypokalemia
10. Hypernatremia
11. Generalized weakness

Transferred to St. Luke’s Rehabilitation Hospital

Clifford L. Tenley, MD received Jordan into inpatient rehabilitation on April 20, 2018 at 1:07 PM, for “ongoing restorative care,” after his recent diagnosis of Shiga toxin producing Escherichia coli(STEC) infection.Jordan and his family were by now well aware and shared with Dr. Tenley that his STEC HUS illness began with the consumption of contaminated romaine lettuce. Dr. Tenley thoroughly reviewed the onset and progression of Jordan’s illness and hospital course before he was discharged. Jordan was currently taking Keppra 1000 mg three times daily, as well as clonazepam 1 mg at bedtime for seizure prophylaxis.

St. Luke’s Rehab Day 2-3

On April 21, 2018, Jordan started physical therapy, and he was alert and oriented and independent of transfers in his room. He had a “ground pass,” but his family had to be with him to use it. Jordan was ambulatory throughout the unit without the use of an assistive device, with his nurse as standby assist only. The nurse noted that Jordan had a steady, balanced gait.

Dr. Tenley came in to see Jordan on April 22, 2018 and was happy to see him doing extremely well. He had no nausea, vomiting, diarrhea, or constipation. He was eating lunch and consuming his entire tray. He was able to take a shower on his own that morning, but he commented that his left leg felt “drunk.” He told the doctor he was hoping to be discharged the next day. Dr. Tenley observed “marked improvement overall in the patient’s condition and status at this time. He likely could be discharged in the very near future if not tomorrow.” Jordan was still anemic on the 20^thwith a hemoglobin of 8.7 and hematocrit of 26%. Dr. Tenley wanted to make sure that he would not be returning to work for at least another week once he was discharged home.

St. Luke’s Rehab Day 4 – going home

On April 23, 2018, case manager Amy Alderman was notified by Dr. Tenley that Jordan was ready for discharge from rehab. She talked with Jordan and learned that he lived in a duplex with his girlfriend and two roommates. Although both she and the roommates would be able to assist him, Jordan was planning to go to his parent’s home when no one was available to be with him the first few days. He stated that he worked at Costco and they were going to put him on light duty until he was ready to get back to his normal, heavier work.

Shannon C. Boyer, NP came in to discharge Jordan from the rehab unit at 3:08 PM. She went over his discharge medications with him and instructions for outpatient follow-up with his physicians, starting with hematologist Dr. Williams on May 1. Jordan’s vital signs were normal and stable, and he was exhibiting no severe symptoms from his ongoing anemia. He was discharged that afternoon.

St. Luke’s Hematology Outpatient Clinic

On May 1, 2018, Jordan presented for an outpatient visit with Travis Williams, DO.  Dr. Williams wanted to see him in follow-up of his thrombocytopenia. Jordan had blood work done that day, which showed a WBC 5.26, hemoglobin 10.0, hematocrit 30.0, and platelet count 182K. Jordan’s main complaint was the side effects of his anti-seizure medications, especially the clonazepam at night, which made him feel very sedated and “quasi out of body experience.” Otherwise, he felt he was regaining his strength after his acute illness. Dr. Williams was happy with Jordan’s hematologic recovery and did not think he needed any other follow-up than a recheck of his CBC in a month.

St. Luke’s Family Health Clinic – Meridian – establishing PCP care

Jordan established care with PCP Rebecca Locke, DO on May 10, 2018. Jordan was interested in getting back to normal, and he explained that he could not drive or drink because of the medication he was on. He hoped to get off the medication.

Dr. Locke reviewed Jordan’s records and observed that he had been placed on Keppra and clonazepam following seizures while hospitalized with E. coli. She went over his hospital course with him, discussing everything that had happened to him. He told her that he had a neurology appointment scheduled for the 23^rd. Dr. Locke documented all of Jordan’s hospital diagnoses and his current state of recovery from each. She wanted to make sure he knew he needed another CBC in about a month, as recommended by the hematologist.

Dr. Locke discussed seizure follow-up recommendations with Jordan and that he needed to follow state laws about a return to driving, which set guidelines for how long he had to wait after a seizure. She was not sure about Idaho’s law, so she advised Jordan to avoid driving until his neurologist gave him the okay. She also deferred to neurology about continuing his anti-seizure medications until they advised it was okay to discontinue them. Meanwhile, she discussed the importance of yearly physicals and to do the follow-up with specialists as recommended when he was discharged from the hospital.

St. Luke’s Neurology – sobering precautions

On May 23, 2018, Jordan went to see Sergei Kashirny, MD for his first neurology follow-up since discharge. Jordan was still on clonazepam at night, and Keppra twice daily. Dr. Kashirny wanted Jordan to continue on his current doses of those medications. If he remained seizure-free for the next 2-3 months, then the doctor was willing to discontinue the clonazepam and continue Jordan on Keppra only. At that point, he planned to repeat an EEG in about 3-6 months to evaluate for any signs of primary generalized epilepsy. Jordan’s mother was with him at this visit, and Dr. Kashirny spent time with both of them to answer their questions and talk about seizure precautions. He did not want Jordan to drive for three months after his last seizure, and he advised him against working on heights/ladders, swimming unsupervised, taking baths (take showers instead)—i.e., to avoid any situation where, should he lose consciousness, either he or someone else could be injured. Dr. Kashirny reviewed “SUDEP” (sudden unexplained death in epilepsy) and emphasized the importance of staying compliant with his anti-epileptic medications. He advised Jordan that, if he had a seizure lasting 5 minutes or more, had back-to-back seizures, or seizures without a prompt return to baseline level of consciousness, 911 should be summoned to take him to the nearest emergency room.

Jordan returned to see Dr. Kashirny on August 2, 2018 for a follow-up visit. He denied any seizure activity or myoclonic jerks. He stated he was currently taking Keppra twice daily (1000 mg each time) and clonazepam 0.5 mg at night. He admitted to some chronic anxiety. Dr. Kirshirny continued with the same plan as delineated at Jordan’s May visit, planning to repeat an EEG to make sure no further seizure activity was present. He advised him to continue taking the Keppra at the current dose but to stop the clonazepam. If he noted any myoclonic activity, he wanted to restart it at the same once daily dose as before. Jordan had his “adult awake/drowsy/sleep” testing done on August 28, 2018 at the EEG laboratory, which Dr. Kashirny interpreted as a normal exam by Dr. Kashirny. His report read: “There are no focal lateralizing or epileptiform features.” In a final comment, he cautioned: “Normal EEG does not exclude a diagnosis of epilepsy. Please correlate clinically with EEG findings.” Dr. Kashirny wanted to see Jordan again in six months.

2019 Neurology Outpatient Visit

On January 22, 2019, Dr. Kashirny saw Jordan in his office for a follow-up visit. Jordan reported no seizure activity or myoclonic jerks, currently on a dose of Keppra short acting 1000 mg twice daily. Jordan was diligent about taking his medication but reported an occasional lapse in dosage. Dr. Kashirny recommended that he continue on the Keppra for at least the next 12-18 months. If he stayed seizure-free during that time, he wanted to repeat an EEG and then slowly discontinue the medication if the test picked up no epileptiform activity. At this point, Dr. Kashirny could not clearly rule out a seizure disorder, potentially “juvenile myoclonic epilepsy.” Dr. Kashirny started him on a slightly increased dose of Keppra, utilizing the extended release form (Keppra XR) of 750 mg to take three times daily (2,250 mg total) instead of the short acting 1 gm tablets twice daily (2,000 mg total). He offered Jordan the option of a one-time nightly dose to improve compliance.

Aftermath

Jordan’s girlfriend Josie reflects on his E. coliO157:H7 HUS illness:

I feel like more than anyone I’ve had to see how much this has affected Jordan, how many aspects of his life have changed, or been lost. Anyone who knows Jordan knows he’s an overthinker, doesn’t just jump into a situation but analyzes every aspect of what could go wrong. He’s good at making sure a situation doesn’t turn bad, if he has a say in it.

Ever since he got sick, he’s had no control in his life. From his job, to coming home, to even mentally and physically, I can see how much this is draining from him. The one place he has the most control is work, but how in control and productive can you be when you’re working around possible epilepsy. His own work duties are handed off to someone else until he’s cleared to perform them. So he’s stuck having to deal and rely on others and put the control in their hands.

He comes home from work exhausted cause his body isn’t used to 40-hour work weeks after lying in a hospital bed for a month without food.

And when he does come home to rest, it’s not home because we’re living in the middle of construction. We didn’t have the time to see all our options, to make sure we were getting into a good living situation. We were trying to avoid being homeless.

I could go on and on. He lost 20 pounds coming out of the hospital but hasn’t had a kitchen to be able to eat a good home cooked meal since he got out. He had to get a new car battery because he wasn’t able to drive his car, so the battery died. He hasn’t been able to drink beer because of the seizure meds he has to take.

Because of those seizures, I’ve watched my boyfriend forget Christmas, I’ve watched him forget time with his family, I’ve watched this man I love forget our anniversary. Because of those seizures, I’ve watched [him] forget his proposal to me twice.And have had to watched how devasted and scared he was that he couldn’t remember. Losing your memory isn’t something small. You’re losing a part of you every time you try to remember. And he has no control in getting those parts of him back.For someone who tries so hard to make sure things go right, to do the right thing, his life shouldn’t look so out of his control.

__________________

[1}        Normal vital sign ranges for the average healthy adult while resting are:

• Blood pressure: 90/60 mm Hg to 120/80 mm Hg.
• Breathing: 12 to 18 breaths per minute.
• Pulse: 60 to 100 beats per minute.
• Temperature: 8°Fto 99.1°F (36.5°C to 37.3°C)/average 98.6°F (37°C)

[2]          Toxic megacolonis a marked enlargement of the colon, esp. the transverse colon. Clinically, tachycardia, and leukocytosis occur. There may be abdominal tenderness, a palpable abdominal mass, confusion, cramping, and change in number of bowel movements per day. Venes, Donald. Taber’s Cyclopedic Medical Dictionary (Taber’s Cyclopedic Medical Dictionary (Thumb Index Version)) (Page 1480). F.A. Davis Company. Kindle Edition

[3]          Neutrophiliarefers to an increase in the number of neutrophils in the blood (e.g., as a result of inflammation, infection, corticosteroid drugs, or malignancies). Ibidat 1620.

[4]          Reference ranges for this lab: WBC 3.80-11K, hemoglobin 13.7-17.5 g/dL, hematocrit 39-55%, platelets 150-420K, BUN 9-20 mg/dL, creatinine 0.66-1.25 mg/dL, AST 17-59 U/L, ALT <50 u>

[5]          Jordan’s haptoglobin was reported as low at <10 mg>

[6]          ADAMTS13 deficiency =<10%. Jordan’s level was 78%. In nearly all patients, aHUS can be distinguished from TTP on the basis of an ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) enzyme activity measurement. It is essential that aHUS and TTP be differentiated quickly, as they require markedly divergent treatments. The standard treatment for TTP is plasma exchange, a therapy that has no role for patients with a diagnosis of aHUS established by ADAMTS13 activity levels. http://www.hematologyandoncology.net/files/2013/02/ho1012_sup171.pdf

[7]          LEV (aka levetiracetam, brand name Keppra) is used in the treatment of seizures; epilepsy; bipolar disorder; neuralgia; new daily persistent headache, and belongs to the drug class pyrrolidine anticonvulsants.”LEV 500 Pill – levetiracetam 500 mg.” LEV 500 Pill – levetiracetam 500 mg. Drugs.com, n.d. Web. 31 Jan. 2017.

[8]          Plasmapheresisis a process that filters the blood and removes harmful antibodies.  It is a procedure done similarly to dialysis; however, it specifically removes antibodies from the plasma portion of the blood.  Antibodies are part of the body’s natural defense system which help destroy things that are not a natural part of our own bodies, like germs or bacteria. In therapeutic plasma exchange, using an automated centrifuge, filtered plasma is discarded and RBCs along with replacement colloid (eg, donor plasma or albumin) are returned to the patient.Kaplan, Bernard S et al. “Current treatment of atypical hemolytic uremic syndrome” Intractable & rare diseases research vol. 3,2 (2014): 34-45

[9]          Hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP) share the morphologic lesion of thrombotic microangiopathy (TMA), characterized by thrombi occluding the microvasculature. The HUS and TTP syndromes overlap clinically; however, certain features have been relied on to distinguish most cases labeled HUS, which is predominantly a disease of children younger than 5 years, from most cases labeled TTP, which is predominantly a disease of adults. Renal manifestations are more prominent than neurologic ones in HUS, whereas neurologic findings are more prominent than renal findings in TTP. Fogo, Agnes B., et al. “Thrombotic microangiopathies.” Fundamentals of Renal Pathology. Springer Berlin Heidelberg, 2014. 135-142.

[10]        Status epilepticus(SE) is a medical emergency associated with significant morbidity and mortality. SE is defined as a continuous seizure lasting more than 30 min, or two or more seizures without full recovery of consciousness between any of them. Cherian, A., & Thomas, S. V. (2009). Status epilepticus. Annals of Indian Academy of Neurology, 12(3), 140–153.

[11]        Vimpat (Lacosamide) is used either alone or in combination with other medications to prevent partial epileptic seizures. https://www.pdr.net/drug-summary/Vimpat-lacosamide-580

[12]         HUS is classified in 2 subgroups: HUS associated with a foodborne infection with Shiga toxin-producing Escherichia coli(STEC+) and atypical HUS (aHUS), or STEC-HUS. McCoy, Nicole, and Donald J Weaver. “Hemolytic Uremic Syndrome with Simultaneous Shiga Toxin Producing Escherichia Coli and Complement Abnormalities.” BMC Pediatrics 14 (2014): 278. PMC. Web. 31 Jan. 2017.

[13]        Eculizumab (Soliris) is the only agent approved for the treatment of non–Stx-HUS. The FDA approved eculizumab for the treatment of non–Stx-HUS in 2011. Eculizumab is a humanized monoclonal antibody against C5 that inhibits the activation of terminal components of complement.Volokhina, E., et al. “Pharmacokinetics and pharmacodynamics of eculizumab in individualized treatment of atypical HUS.” Pediatric Nephrology. Vol. 31. No. 10. 233. Springer, 2016

[14]        TPN by definition is nutrition given intravenously. It typically consists of dextrose, amino acids, emulsified fats, trace elements, vitamins, and minerals to patients who are unable to assimilate adequate nutrition by mouth.Because TPN solutions are concentrated and can cause thrombosis of peripheral veins, a central venous catheter is usually required. Venes, Donald. Taber’s Cyclopedic Medical Dictionary (Taber’s Cyclopedic Medical Dictionary (Thumb Index Version)) (Page 1650). F.A. Davis Company. Kindle Edition.

Republished with permission from Bill Marler and Marler Clark. Copyright (c) Marler Clark LLP, PS. All rights reserved.