by Barbara Ebel
Finally, she did pick up her phone. Dialed her family in Tennessee. Talked until she felt she’d spent the whole morning with them. She even spoke with her sister who told her, “Just because you’ve finished six measly weeks on surgery, don’t become more of a know-it-all than you already are. Just think about Dad. He’s been doing it for years and years and he says he still doesn’t know everything.”
She didn’t know Nancy had that kind of wisdom to give her such advice. But she didn’t mind it because it was true.
-----
On Monday morning, Annabel drove to the surgery department rehashing the challenging test she had taken. She even questioned some of the answers she thought she had responded to correctly.
She parked and made her way into the overly air-conditioned building and went up to the second floor. There was already a group waiting for the promised 9 a.m. results and, within minutes, Da’wan and Ginny showed up.
As Annabel leaned against the wall, Bob turned the corner and strutted down the hallway. He wore a big grin and came directly to her, his eyes widening with pleasure as he grabbed her arm and pulled her away from the others.
“You can’t believe what I just heard,” he said excitedly. “I overheard some surgery residents in the cafeteria. Dr. Mack has been placed on probation!”
“Really?” she beamed.
“Oh yeah. Apparently a bunch of stuff has been accumulating about him. Can you believe it?”
Annabel nodded. “I think I can,” she said. “It’s nice to see someone get what they deserve.”
“Especially for your sake. He was such a snake to you.”
“Thanks, Bob. How about we go see if we’re marching on to psychiatry together?”
“Let’s go,” he said. They turned and walked into the office where the secretary was handing out envelopes.
Da’wan passed them and then Ginny. “We’re safe,” Da’wan said.
“I bet you’re better than safe,” Bob said. You probably got the highest score.”
Da’wan shrugged his shoulders. “Thanks for the confidence. Maybe I’ll see you both on another rotation.”
Bob stepped up and tore open his envelope without flinching. “Phew,” he said. “I’m good. And I got the two extra credit points due to all our teamwork.”
Annabel stepped to the side and opened hers. One sheet displayed the breakdown of scores; overall, hers was a ninety. She could hardly believe it but knew it was because the final exam score of ninety-four as well as the perfect clinical evaluation had brought up the poor results of her first test. She read Dr. Burk’s comments:
This student showed outstanding fortitude when faced with formidable circumstances during this rotation. She withstood bullying in a professional manner and showed compassion and understanding for her patients.
Over and above this, the morbidity and mortality during the last month and a half were higher than normal and Dr. Tilson showed extreme resolve to find answers to the clinical problems which plagued our patients. She makes us proud to know that young physicians like her will be taking over the future of medicine.
Tears filled her eyes and she had to take a big breath to keep from crying.
“Well?”
She slipped the papers back into the envelope and looked at Bob.
“We’re outta here,” she said and nodded. “Let’s stop at the med-school bookstore and pick up psychiatry books.”
Bob gave her a thumbs up. Downstairs, he opened the door for her, they walked out into the sunshine, and strolled across the campus without a care in the world.
Epilogue
Annabel sifted through her small closet to select her best professional outfit. She didn’t want to dress as if going to a party or on a date; today she had to look like an accomplished businesswoman or physician without a white coat. The fact that the surgery department, anesthesia department, and the scientific representatives from the FDA and drug manufacturer of Legammadex had even invited her and Wilbur Gill to their crucial meeting was like having them raise a sword gently over their heads and placing it on their left shoulders.
Her hand rested on a simple black skirt and then a burgundy blouse tapered at the waist. The darker colors would be fine since it was the latter part of fall. She pulled out the only black shoes she owned, short heels with a strap and rounded front end. She dressed and put on an amber necklace which hung in the open area of her neck. After applying a little makeup, she massaged mousse into her hair. Her natural waves now shined and fell softly around her face.
After her dreary drive and hurried pace from the parking lot on the cold, damp November day, her nervousness ramped up when she got off the elevator and opened the door to the anesthesia department. Looking up from her desk, the chairman’s secretary smiled and pointed to the conference room.
She held the door as others came in behind her. The anesthesia group already sat at the table: Dr. Parker, Wilbur Gill, and Dr. Richie, the anesthesiologist who had come to her rescue during her paralysis in the PACU.
“On your way over, help yourselves to coffee,” Dr. Parker said. “A dark roast to get you all going.”
Annabel declined and, seeking the solace of someone with less hierarchy than the chairman, she took a seat next to Wilbur. The head of the surgery department, Dr. Allen, walked in along with her previous attending, Dr. Pittman. Lastly, Robby came in with a stranger she didn’t recognize.
She hadn’t seen Robby since her last day on the surgery rotation. It had saddened her that she hadn’t bumped into him the day of her final exam or the day the students huddled in the office to pick up their grades. However, that had made it easier to try and work him out of her thoughts. Annabel felt sure that she had been just another student to him, one that came and went like the groceries in her pantry.
Still, she watched him as he poured a cup of coffee. It seemed as if he wore a halo of surgical knowledge and that he had important agendas on his mind. This was where he belonged: An academic institution where he made a difference and had earned the confidence of those around him, especially her.
After turning to the guest next to him and pouring the man’s coffee as well, Robby turned and scanned the faces at the table. Her adrenaline kicked up a notch and her heart quickly pumped blood to her brain where thoughts of him touching her hair in the office made her shiver. His eyes twinkled when he saw her and they both smiled a hello.
Robby and the stranger sat several spots away; now there would be no chance to even engage in small talk with him. She looked down with disappointment as Dr. Parker walked over to the door.
“We’re not to be disturbed now,” the chairman said to his secretary and closed the door; he resumed his spot at the head of the table.
“Everyone knows each other here except for our two guests whom some of us have been in contact with. I’d like to introduce Dr. Brewer next to Dr. Burk. He is an M.D. working for the FDA in both a scientific and administrative role.”
A tall, bald man with a weathered complexion stood for a second and Dr. Parker went on. “On the other side of him is Dr. Strickland. She is a PhD doctor who has a scientific and executive role over a research department of the drug company that makes Legammadex. She is also one of their liaisons to the public and the FDA.”
Dr. Parker went on with a short description of all the doctors in the room for the benefit of both Dr. Brewer and Dr. Strickland and then Dr. Brewer leaned forward and spoke.
“As opposed to the awful stories you hear about bad drugs and cover-ups of drugs that get into the market and cause a great deal of harm, it is with quick action that both Dr. Strickland and I handled the situation that this group presented to us several months ago. We want to thank you for your scientific curiosity about the etiology of the postop paralysis you were encountering. It is because of your original calls to our organizations that prompt research into the problem was undertaken and, of course, the drug was immediately recalled. Although we are still gaining more insight, we came to persona
lly tell you the conclusions of what we’ve found. It’s interesting material … the findings of which never surfaced with testing before the release of the drug. Otherwise, FDA headquarters would have never approved the drug.”
Knowing they both had provided input regarding this serious issue, Annabel glanced sideways at Wilbur and they gave each other a small grin.
Dr. Brewer turned towards Dr. Strickland. “These anesthesiologists and surgeons are going to be impressed with what Legammadex pulled off.”
“Thank you, Dr. Brewer,” she said. “I enjoy talking to groups like this who understand the pharmacokinetics and pharmacodynamics of these anesthesia drugs. But do stop me if you lose me at any point.” She nudged the small glasses on her nose which mirrored her thin frame and Annabel figured she couldn’t be more than a size two. A little lady in a big job.
“So,” she said, “the reason we’re all here is because of the drug which came into question, Legammadex, which antagonizes nondepolarizing neuromuscular blockade with only rocuronium and vecuronium. As a pharmacology reminder to the younger clinicians, rocuronium and vecuronium are nondepolarizing neuromuscular blocking drugs which act by competing with acetylcholine for certain subunits at the postjunctional nicotinic cholinergic receptors. That prevents changes in ion permeability.” She scanned everyone’s face and continued. “And that prevents depolarization at the neuromuscular junction and skeletal muscle paralysis ensues.”
She took a sip of water while Dr. Parker spoke up. “It is the manipulation of nerve impulses at the skeletal muscle junction which caused me to write several papers on the subject,” he said.
Dr. Strickland nodded. “Yes, and we routinely monitor the work coming from the actual clinicians. Anyway, after paralysis sets in - as you know - we need a drug to reverse those effects. Traditionally, there have been three agents on the market. But then Legammadex came along which offered something substantial that the others didn’t; it can reverse a deep block, a very valuable clinical addition to the anesthesiologist.”
The wiry woman nudged her glasses again and looked at the faces around the table. Annabel appreciated the pharmacology overview especially since now the woman was headed into unfamiliar territory with the troublesome new drug.
“The other big difference with Legammadex,” she continued, “is that it works differently than the other agents on the market. Those other three drugs increase acetylcholine, the needed neurotransmitter at the neuromuscular junction, allowing return of skeletal muscle function.
“Yet, instead, Legammadex forms a complex with rocuronium and vecuronium. By making that complex, the muscle relaxants are removed from the neuromuscular junction and the return of muscle function is accomplished. That complex is then simply metabolized.”
“It seems like such a simple and effective drug interaction,” Robby said. “It’s a wonder it wasn’t discovered before.”
“So true,” Dr. Brewer with the FDA said. “And all studies went along fine so we gave the drug its approval for market. But then you all became suspicious. All the blood work tested between our labs and even further investigation by the forensic pathologist and your hospital pointed to a problem with the drug because vecuronium or rocuronium showed back up in the blood.”
“And may I interject,” Dr. Parker said, his hand rubbing his old acne scars. “I have a list here of the patients tested who had all received one of the two muscle relaxants and then Legammadex for reversal.”
“Please tell us from surgery who was confirmed,” Dr. Pittman said. “It must be most of the patients we fretted over.”
“I have here patients’ names of Hardy, sixty-five years old, we did a lap choly; Kingman, a twenty-eight-year-old, a burn unit patient; Vega, who was only twenty-five and had a ruptured appendix; and Simmons who came back due to an inguinal hernia repair. We also found, due to good investigative work, a few other patients in Ohio, Kentucky, and Tennessee.”
Annabel immediately thought about her conversation with her Uncle Casey. As a paramedic, he had transported a patient to another hospital who had just had surgery and the patient died with an unclear explanation.
“May I ask a question?” Annabel said.
Dr. Strickland smiled. “Dr. Brewer and I heard about you. You must be the young female student who brainstormed these patient incidents as well as the only medical team player who became a patient herself.”
“Yes I am,” she managed to say with a grin. “I almost left in a body bag.”
“I can answer any questions later,” Dr. Strickland said. “But, sure, what is it now?”
“Isn’t it odd that the cases only showed up in this cluster of states?”
Dr. Strickland glanced at Dr. Brewer and then back to Annabel. “Precisely. Excellent observation. We’ll talk about that later.”
“So getting back to the pharmacology,” Dr. Strickland said, “the beauty of our new drug was the bonding to the muscle relaxants in question which effectively made a new compound which could not provide muscle paralysis. But lo and behold, we discovered there is a way that that bond can be broken. Which means that later on - such as in the PACU - if that bond is severed, then the muscle relaxant is let loose again on the neuromuscular junction to re-paralyze the patient.”
Annabel glanced over at Robby as he gave several big nods on hearing the news. Wilbur mumbled “Wow,” and Dr. Parker rolled his chair closer to the table and shook his head.
“Even though you and the FDA have shared your initial thoughts with me,” Dr. Parker said, “it’s amazing what unforeseen dynamics can occur with drugs.”
“And both organizations are sure about this?” Robby asked.
“Absolutely,” she said. “And the next dilemma was what was causing it because I can assure you that this problem never occurred during our testing.”
“And we are thorough in our scrutiny,” Dr. Brewer said. “Legammadex would have never gotten in anesthesiologist’s hands if we weren’t sure about its safety.”
Annabel now understood why she became re-paralyzed but now she speculated as to why it only happened to a few, not all, patients who had received it. But she didn’t have a clue.
“Now,” Dr. Brewer said, “this gets complicated and we were shocked to find out what we know. The anesthesiologists will have a better understanding of what we found because they are the most knowledgeable of the rare anesthesia problem called malignant hyperthermia. That potentially lethal entity exists due to a genetic abnormality and that is exactly what we believe occurs with patients exhibiting re-paralysis with Legammadex.”
Dr. Strickland took a deep breath while all eyes stayed glued on her. “These people,” she continued, “carry a gene mutation which is inherited as an autosomal dominant trait. We have given it a name – LGM1 gene mutation – and the people who carry it have an enzyme which breaks down the Legammadex-nondepolarizing neuromuscular blocker bond. By our estimates, we believe that in the general population of the United States, one in one-hundred thousand patients have this gene mutation.”
The chairman of surgery had not said much but he sat back in his chair, twitched his pointy nose, and said, “Amazing. How complex. And our accolades to all the research teams that discovered it. It’s too bad it didn’t happen sooner, but who would have guessed?”
“Yes,” she said. “And to answer Dr. Tilson’s wise question - just like malignant hyperthermia or MH - there is a geographic hotspot. In MH, it’s Wisconsin, Michigan, and West Virginia. With this problem, our investigation points to Ohio, Kentucky, and Tennessee as the population more at risk for the LGM1 gene mutation. Which also explains the rash of patients we’ve had here.” She rubbed her hand behind her neck as she considered one more point. “And another similarity between the two entities is that the first exposure may not trigger an event. For instance, Mr. Simmons only became re-paralyzed after a repeat exposure to Legammadex.”
A silence ensued. It was a lot to absorb; another medical syndrome that became a reality because of a
drug that was invented by a clever pharmaceutical company. A drug that was supposed to enable the surgical process now became one to avoid. Unless, of course, trouble was taken to screen all persons going to surgery for the LGM1 gene. But Dr. Brewer assured them all that that would be cost-prohibitive. The drug would fade into the background unless it was changed into some other formulation.
“This has been of utmost interest to all of us,” Dr. Parker said, “and we thank you for coming personally to share this with us. What follow-up is going to be done as far as the patients who suffered bad outcomes from the drug?”
“Both the FDA and us,” Dr. Strickland said, “are giving families full disclosure. One has already been in contact … their lawyers, that is. We know there will be forms of retribution and attorneys involved, but we will divulge what we know and when we learned it. Hopefully, our honesty and sincerity of putting a good drug on the market will be taken into consideration.”
After another ten minutes, no more questions were forthcoming and Dr. Parker called the meeting to an end. “Dr. Allen and I will be taking our guests on a short tour of the medical campus and then on to a fine restaurant in Cincinnati. Thank you all for coming.”
Everyone stood and, as Annabel talked with Wilbur, Dr. Strickland walked over to her.
“Dr. Tilson,” she said, “perhaps you wouldn’t mind adding one more thing for the wrap-up of our research. A blood sample to verify you carry the LGM1 gene. I think you’re the only person alive who received Legammadex and who we believe carries the gene.”
“No problem,” Annabel said.
“Thank you,” she said. “And all the best with your clinical rotations.” She walked away and Annabel realized Wilbur had also left.
As the group discussed what they had heard and exited the conference room, Annabel picked up her small purse and then looked across the table. Dr. Burk talked with Dr. Pittman but occasionally looked over at her. Pittman left and, surprisingly, Robby walked towards her end of the conference table.