With more than 124,000 people in the U.S. waiting for an organ transplant, new organ procurement methods need to be established.

The Institute of Medicine issued a statement in 2005 suggesting that uncontrolled donation after circulatory determination of death (uDCDD) could help to increase the availability of organs for donation.

uDCDD occurs when a patient suddenly experiences cardiac arrest outside of the hospital, resuscitation is unsuccessful and the organ donation is possible. In this situation an organ preservation unit (OPU) would need to obtain consent from loved ones and assess patient eligibility for organ donation.

An article published in the November edition of Annals of Emergency Medicine looked at the New York City out-of-hospital uDCDD program from December 2010 to May 2011. This program hoped to obtain kidneys from patients who died suddenly from cardiac arrest outside of the hospital.

A typical situation expected during this study would be as follows: EMS would arrive on a scene of a cardiac arrest patient. Once the patient was determined to be nonresponsive to resuscitation, they would conduct a basic screening to determine organ donation eligibility. If appropriate, an organ preservation vehicle would be sent to the scene. If the patient met the strict inclusion criteria, they would preserve the organs in vivo using a portable ventilator and chest compression device until the organs could be procured in a hospital setting.

In the NYC uDCDD program, the OPU responded to 124 cardiac arrests. The OPU only interacted with 9 authorized parties (loved ones able to provide consent). Four of the 9 authorized parties were willing to authorize donation. The other 5 reacted in a positive and favorable manner but withheld consent.

Staff was required to keep thorough documentation of public interactions to the OPU as well as personal reactions. From the study, 837 operation notes were collected which proved to be valuable.

Unfortunately, no organs were recovered during the study period due to strict criteria and an unavoidably complicated protocol.

After reviewing operation notes, the author concluded that in lieu of the small sample size, the public’s perception was more favorable than anticipated showing promise for future uDCDD programs.

Articles

Surgical Rounds

It's about time for new methods for organ procurement.

Mobile Organ Preservation Vehicles: The Public's Perception

An awakening in the midst of surgery is a patient’s and an anesthesiologist’s nightmare.

British scientists have developed a new way to prevent that.

By measuring brain waves, they reported, it’s possible to titrate the appropriate amount of the drug needed to put a patient under. 

This discovery is important because of the “considerable variability” in individuals’ responsiveness to anesthesia, the University of Cambridge team said in a study published in the January 14 issue of PLOS Computational Biology.

“By measuring their behavioral responsiveness and the amount of sedative in their blood, we found a striking pattern: the strength of their brain networks before sedation predicted why some participants lost consciousness while others did not, despite registering similar blood levels of the drug,” senior author, Tristan Bekinschtein, PhD, of the University’s Department of Psychology, and his colleagues reported.

“By uncovering underlying signatures of this variability, our findings could enable accurate brain monitoring during anesthesia and minimize intra-operative awareness.”

The team used high-density electroencephalography (EEG) to study how 20 healthy adults’ brain networks changed as they were sedated by propofol.

EEG tracking during sedation hasn't been common because of the lack of robust EEG markers that show the loss and regaining of consciousness, according to the study. That practice could change with the group’s discovery of such markers.

“EEG machines are commonplace in hospitals and relatively inexpensive,” Bekinschtein said. “With some engineering and further testing, we expect they could be adapted to help doctors optimize the amount of drug and individual needs to receive to become unconscious with increasing their risk of complications.”

Using nine male and 11 female test subjects, the researchers looked at the correlation between blood levels of propofol and alpha and delta brain waves.

The subjects received increasing doses of the anesthetic as they were asked to press different buttons when they heard a ping or a pong, while an EEG tracked their brain waves. At the maximum dose, 13 maintained consciousness and continued pushing buttons while others were unconscious. Both before and after the anesthesia, the alpha networks were most predictive of which group lost consciousness.

These results “if replicated and verified in the clinical context, could contribute reliable applications of brain monitoring for tracking and accurately modulating consciousness with anesthetics during routine surgery,” the study concluded.

An awakening in the midst of surgery is a patientâ€™s and an anesthesiologistâ€™s nightmare. British scientists have developed a new way to prevent that.


Waking Up During Surgery

Patients have often been told to avoid ibuprofen and other nonsteroidal anti-inflammatory drugs (NSAIDs) before or after surgery due to an increased risk of bleeding.

However, new evidence suggests ibuprofen does not in fact increase the risk of bleeding following plastic surgery procedures.

Researchers from the University of Michigan believed ibuprofen could provide safe and effective pain control for selected plastic surgery procedures, while avoiding the higher risks and costs of some other pain medications.

To compare ibuprofen with other pain medications for patients undergoing plastic surgery-related operations, the research team conducted a systemic review of four studies in which 443 patients were randomly assigned to receive ibuprofen or other medications such as acetaminophen, acetaminophen plus codeine, or the prescription-only NSAID ketorolac.

The procedures that were studied included cosmetic facial surgery, breast cancer surgery, hernia repair, and skin cancer surgery and reconstruction.

All the studies began ibuprofen administration of 400 mg every four hours either before or immediately after surgery and continued for at least one week.

Findings reported good pain control across study medications. Ibuprofen and the other treatments also showed similar bleeding risks. The rates of “surgically significant postoperative bleeding” were 3.5% with ibuprofen and 4.1% with other treatments.

The researchers did acknowledge their study was limited to procedures were bleeding and hematomas were easily traceable.

Nonetheless, the team believed for plastic and dermatological surgery procedures for smaller areas, ibuprofen could provide good pain control without increasing the risk of bleeding.

The authors concluded, “OTC analgesics like ibuprofen are more cost effective given their effectiveness in pain control, well-established public tolerance, and low-risk qualities for abuse.”

Ibuprofen Can Help Bleeding Risk After Plastic Surgery

Former cancer patient Thomas Manning from Halifax, Massachusetts, is the first man in the US to undergo a penis transplant.

After having had part of his penis removed in 2012 following a penile cancer diagnosis, surgeons from Massachusetts General Hospital (MGH) performed the nation’s first genitourinary vascularized composite allograft (GUVCA) transplant earlier this month.

Led by Curtis Cetrulo, MD, and Dicken S.C. Ko, MD, a team of nearly 50 medical personnel, including plastic surgeons, urologists, and anesthesiologists, participated in the “marathon operation.”

The donor organ was from a deceased donor through the New England Organ Bank.

The 15-hour operation involved surgically grafting microscopic vascular and neural structures of a donor organ onto Manning’s comparable structures.

While the procedure took 15 hours, preparation for this landmark operation involved approximately 3½ years of research and collaboration across several medical divisions in MGH Transplant Center.

The possibility of successfully undertaking a GUVCA transplant manifested in 2012 after Cetrulo and the MGH team completed their first hand transplant. Both Cetrulo and Ko worked closely with the New England Organ Bank to develop key strategic surgical approaches to help patients suffering from genitourinary injuries.

The surgeons explained that the three primary goals of GUVCA transplants were:

·      Reconstruct external genitalia to a more natural appearance

·      Potentially achieve sexual function

Ko did add that while sexual function was a goal, reproduction wasn’t — surprisingly, because of ethical issues and concerns of who the potential father could be.

Beyond medical concerns, genitalia loss can heavily impact an individual’s identity. The psychological aspects of genitourinary injuries can truly be devastating, so members from psychiatry and social work divisions are often involved in patients’ recovery processes.

Manning, 64, continues to recover well, with blood flow established to the donor organ and no signs of bleeding, rejection, or infection.

However, Manning will need to take immunosuppressing drugs for the remainder of his life to limit any chance of rejection.

Although he is still in the early stages of the “post-surgical healing process,” Manning’s doctors are “cautiously optimistic” about his recovery and anticipate that he will regain function.

He should be discharged in approximately three to four days, and will be sent to a different facility to monitor his recovery.

Ko remarked in a news release, “These proof-of-principle cases will help establish the techniques used in this procedure and will forge the path to future treatment of patients with significant pelvic and genitourinary tissue loss related to cancer, trauma, or infection. We are delighted to have taken the first steps to help those patients who have suffered silently for far too long.”

Manning had been inspired to talk to others with similar injuries. According to Cetrulo, “We hope to open this up to other patient populations, including wounded warriors.”

“Today I begin a new chapter of my life with personal hope and hope for others who have suffered genital injuries. In sharing this success with all of you, it’s my hope we can usher in a bright future for this type of transplantation,” Manning said in the news release.

Reports show there have been at least two other penis transplants across the globe. A man in Tygerberg Hospital, Cape Town, South Africa, underwent a successful transplant in 2014, while a Chinese man experienced an unsuccessful surgery in 2006.

Both Johns Hopkins Hospital and Brigham and Women’s Hospital are approved to perform the procedure.

Surgical Milestone: Mass Gen Completes Nation's First Penis Transplant

Surgery causes high levels of stress in 50% to 75% of children, but humor and laughter can help children cope with pain and stress.

As such, many hospitals employ medical clowns to bring joy and happiness to patients. Previous research had shown clowns improved the self-perception of children undergoing gastroenterology procedures or sexual abuse exams. Another study used clowns to reduce pain and anxiety associated with venous blood draws. Previous research has not explored the impact of medical clowns on surgery-related medical costs.

Furthermore, an article published ahead-of-print in the Journal of Paediatrics and Child Health indicated that medical clowns reduced pre-operative anxiety and post-operative pain, shortened overall medical costs, and reduced time to return to normal activities after outpatient penile surgery in children.

The study randomized eighty children between two and 16 years old undergoing penile meatotomy in a 1:1 ratio into clown-inclusive and clown-exclusive arms. The study excluded previously anesthetized children. The researchers quantified preoperative anxiety with the 22-item modified Yale Preoperative Anxiety Scale Instrument and pain with the “Face and Legs activity, Cry, Consolability” scale for patients younger than three years old and Wong-Baker Faces scale for older children.

The clown-accompanied patients reported less anxiety, required less time for induction of anesthesia, and used less time in the operating room (OR).

Patients at the researchers’ institution were 96% receptive to the inclusion of clowns into the pre-operative workflow but Vagnoli et al. documents clowning in a less receptive environment. Only one family in the clown arm had a negative impression of the clown.

This institution’s clowns undergo education on the treated medical conditions, surgical anatomy, functions of the OR (e.g. garbing), and roles of the members of the OR team. Clowns reduced OR time by 6% and saved $467. Additional revenue can be generated by scheduling more procedures per OR as well.

The authors concluded that clowns reduce pre-operative stress, post-operative pain, and expedite anesthesia induction in pediatric penile meatotomy patients, and they call for additional research on larger and broader surgical patient populations.

Surgery causes high levels of stress in 50% to 75% of children, but humor and laughter can help children cope with pain and stress. 

Surgery for Kids: Send in the Clowns!

Surgery after fewer than three episodes of uncomplicated diverticulitis seems to be common even though most guidelines recommend delaying elective colon resection. This situation may be influenced by an increased likelihood of younger patients, availability of laparoscopic procedures, and appreciation for smoldering (non-recovering) diverticulitis.

Researchers from several institutions in the state of Washington looked for diverticulitis episode patterns in surgical candidates in an attempt to discover why early surgery is so common. Their study, published in JAMA Surgery, identifies several factors.

This investigation retrospective cohort study covered four calendar years, from 2009 through 2012. All study subjects were immunocompetent adults with incident, uncomplicated diverticulitis who underwent elective colectomy.

The researchers identified 87,461 patients with at least 1 claim for diverticulitis; 6.4%

(n = 5604) underwent resection and 3054 were eligible for the final cohort.

Before undergoing resection, the average patient had been admitted once, had 2 outpatient episodes, and had filled 0.5 prescriptions for antibiotics for diverticulitis.

Patients' average age was 47.7 years, and this was identical to patients who delayed. Based on inpatient claims only, the vast majority of patients (94.9%) had surgery after fewer than 3 episodes. That number fell to 80.5% if outpatient claims were included. After considering all types of diverticulitis claims including antibiotics, the researchers classified 56.3% of elective resections as "early."

Patients undergoing early surgery with less likely to undergo laparoscopy, and their pre-surgical episodes occurred less frequently (157 days apart) than patients who delayed (96 days apart).

Enrollment in a health maintenance organization or capitated insurance plans reduced early surgery rates by about 14%.

The researchers note that they did not consider patient factors. Burden of disease, especially quality of life or anxiety about future episodes, is a potential factor that may encourage surgeons and patients to consider and accept early surgery.

It has become increasingly common for patients having experienced as few as three episodes of diverticulitis to opt for colectomy. A study examines the efficacy of younger, less frequent sufferers receiving the surgery earlier than guidelines typically recommend.

Diverticulitis: Why Operate Early?

Editor’s Note: Scott Sigman, MD, is a team physician for the University of Massachusetts Lowell. He is also an appointee on the Governor Charlie Backer’s special commission to establish a pain management program for the Commonwealth of Massachusetts. Although he was not an author on the study discussed below, he is a spokesperson for the Choices Matter campaign and frequently offers his patients non-opioid alternatives to combat the epidemic — which led to his interest in this research. The study included 500 adult patients who had either soft tissue or orthopedic surgery within the previous year and were given short-term postsurgical prescriptions, defined as up to 10 days, and the 200 surgeons who performed the procedures in the United States.

MD Magazine: Before this new research was conducted, what did doctors think the rate of opioid addiction and dependence was after surgery?

SS: The number I’ve been quoting, and I’ve been doing this for quite some time, was always one out of 15. That’s where most of the studies have sort of landed. I was very surprised in this survey to see that it was really closer to one out of 10 that patients were describing dependency on narcotics, which it sort of helps to explain a little bit as to why this opioid crisis was really blown out of control at this point.

MD Magazine: What are some of the populations that doctors are most concerned about for opioid addiction and dependence?

SS: It’s interesting. Another very important point out of the survey which I saw which was really fascinating is that 90% of prescribing surgeons felt a pressure to prescribe more narcotic. That really jumped off the page for me. I’m sure you’re aware with the HCAHP scores that were put together with Obamacare and CMS in the attempts of trying to sort of manage patient care with surveys and patient reported outcomes. And two of the questions on that survey really dealt with pain. And the questions were, do you feel that you’re adequately, were you adequately covered with your pain management through your stay. So, in order to get a better HCAHP score, right, if you get a better HCAHP score, CMS will then actually pay you more money for the procedure because they feel that the patients are more satisfied, so therefore you earn more money for the actions you’ve taken. And so doctors felt compelled to write additional narcotic prescriptions because they wanted their patients to be able to report on the survey that their pain was managed appropriately which is obviously the exact opposite of what we’re trying to accomplish at this point.

MD Magazine: You said that the physicians in the study felt more compelled to prescribe more narcotics because they wanted their patients to be satisfied when they did fill out the survey. Do you think that this translates to everyday practice where doctors feel that pressure from their patients?

SS: Yeah, I do. So let me tell you what I’m doing in my clinical practice which has really changed for me. So I have a conversation with every single patient that walks through my door that winds up getting scheduled for elective surgery in advance of their surgery. And what I do is I specifically express to the patient about what my expectations are for what their pain will be. I tell every patient, it’s not possible for me to take away all of your pain. We’re going to make you comfortable. We’re going to get you through this. You will have some pain, it will be manageable, and here’s how we’re going to do it. And then I ask the patient, what are your expectations? Many times they’re saying, well, I have a niece, nephew, or a coworker who became addicted to medication, maybe even died in this crisis. I want to know, what options are there? And, for the most part, patients are really pleased, number one to know that I care and that we want to make sure that they get through the surgical experience in a safe fashion. They’re appreciative to know that there are options that are out there. And so the good news is for me is that I know this and I do this with every single patient. But there may be some doctors out there that aren’t completely familiar with all of the various alternatives that are out there.

MD Magazine: Do you think that it’s up to the physician or the patient to bring up the non-opioid possible approach or does the responsibility fall equally?

SS: Equally, 100%. I think we absolutely need to empower our patients to let them know that they have options, and we also equally need to make sure that our physicians are educated into the various alternatives. I saw a patient come down my hallway today. She’s 14 days after a total knee replacement. She is taking Tylenol, oral Tylenol right now. She’s walking without a cane or a knee mobilizer. At the time of her surgery, we injected a medication directly into the surgical site. We also gave her IV nonsteroidal medications. We gave her oral anti-inflammatories, and literally she walked home two days after surgery and is where she is at this point. And I firmly believe that these alternatives to opioids can be used quite successfully, even in the most major orthopedic surgeries.

Whenever I have this conversation about opioids, there are patients in chronic pain that are being successfully treated with opioids by pain management specialists for chronic pain scenarios — cancer, fibromyalgia, or other chronic pain syndromes. And those patients need to get continued care. I am not advocating that all opioids should be wiped out of the market. We want to care for those patients. We want to message that loud and clear.

MD Magazine: The survey results indicated that less than 25% of patients discussed non-opioid pain control options for surgery with their doctors. How can a physician better initiate that conversation with their patients?

SS: In my clinical experience, what I do, you literally have to talk about it with every single patient. And it is not done the day of surgery. It’s not done five minutes before the patient is rolling into the room. The conversation is had the minute that a doctor is consenting a patient for surgery in their preoperative operation in the clinic.

Now, some of these alternatives, to be perfectly honest, are not available in some hospitals across the country because of cost concerns. Because these medications that we’re using, which are opioid alternatives, are actually significantly more expensive than the opioids. Now, interesting, in the State of Massachusetts, I just recently had a conversation with the Health and Human Services Department, and over $300 million per year is now being spent on the Mass Health Medicaid population for patients that are in substance use disorder, $300 million a year. That’s a tremendous amount of money that’s being spent on the consequences of this epidemic. So I feel quite strongly that we need to be spending money on the front side of this epidemic to prevent the wave of patients that are coming into the system.

MD Magazine: How do you think that this new finding, that it’s not really one in 15 patients who become dependent but one in 10, will change the way that doctors treat their patients?

SS: I think it’s proving it’s even more urgent at this point now that we get this message across because we’ve all heard these stories. I mean, the 18-year-old kid that comes in. He’s a college athlete, he’s got a Division I scholarship, he has a torn ACL, he undergoes surgery, he’s prescribed narcotics by his doctor, and six months later he’s dead of IV heroin, or now Fentanyl which is the latest drug that we’re seeing used on the streets. And these kids are literally dead. It is urgent that we get this message across to all patients and doctors that these options are available. One out of 15 to one out of 10, I was really blown away by that number. It gives me a better sense of why this epidemic is really blooming as much as it is at this time.

MD Magazine: Can you tell me a little bit about the Choices Matter program?

SS: The Choices Matter program is specifically designed to empower patients to give them the options, to let them know that there are options to opioids during your surgical intervention. We get the fact that, again, going to a doctor can be a scary event. Most of the time you want to trust and just listen to the doctor, but what we want to do is let the patients know that you can help direct your care. Express to the doctor that you have questions and concerns. And, for example, you might not know what questions to ask, so there’s a website that’s been developed through the Choices Matter campaign that’s called planagainstpain.com. And you go on that website, click, fill out a couple of questions. There’s about 11 questions. It’s a survey and it will then allow you to print out a sheet of paper with a few questions that you can bring to the doctor, specifically to say, hey, doc, what alternatives are there?

I talk about pain as sort of the storm of pain. The worst of the pain in any surgical intervention is within the first 72 hours. So, if you can reduce that pain syndrome in that 72 hours, it’s not like at the end of 72 hours it’s just as bad as it was at the surgery, all of those pain generators have been flushed out of the system and patients get a much softer landing. They have much less need for postoperative narcotics and medication, and they can really navigate through the surgery quite well.

MD Magazine: Can you tell me about Gabrielle Reece’s (pictured above) role in the program?

SS: Gabby Reece is this amazing professional athlete. She’s the healthiest person I’ve ever met in my life. She really wanted to try and minimize her experience and exposure to medications. And basically she blew out her knee over multiple years as a professional volleyball player, and it got to the point where she just really no longer handled it anymore and she required a knee replacement. And about two months ago or so, she underwent a knee replacement and she basically said to the doc, look, I want to minimize narcotics. She took a couple of pain pills on the first day or so, but she basically left the hospital not taking any postoperative narcotics or prescriptive medications. And, look, she’s a professional athlete. She was able to tough through it through true grit, if you will, but she’ll be the first one to tell you that she struggled. And she’s struggling. She’s had a knee manipulation now to try to regain her motion.

She’s making slow and steady progress to recover, and if you ask her, she’s like, wow, had I know that these options were available, I really would have pushed my doctor to look for these other opioid alternatives to try and get me through this in an even better fashion. So she didn’t even know it was available. When she sort of got wind of this Choice Matters campaign, it fit perfectly into her and her being as a person, her lifestyle, the way she lives. And she wants the message to patients to say, look, you don’t have to do what I did. You don’t have to tough it out. If you don’t want to take narcotics, there’s great options that can help to get you through this. And she’s been a real leader and great spokeswoman in trying to message that for us.

Scott Sigman, MD, discusses recent study results that show more people become dependent on prescription drugs following surgery than previously thought â€“ which is why his involvement in the Choices Matter program is so important.

Opioid Dependence After Surgery Is Even Worse Than Physicians Thought

Long surgeries can cause neurological damage in babies, fetuses, and toddlers.

When infants, young children, or pregnant women need surgery the risk of brain or neurologic injury from anesthesia has long been a concern.

In a Drug Safety Communication sent today the US Food and Drug Administration (FDA) said that anesthesia administered for more than three hours may adversely affect the developing brains of children younger than 3 years old and the fetus in pregnancies that are in the third trimester. The same is true for repeated surgeries.

That includes 11 drugs that block N-methyl-D-aspartate receptors or potentiate gamma-aminobutyric acid activity, or both.

“No specific medications have been shown to be safer than any other” the FDA noted.

“We recognize that in many cases these exposures may be medically necessary and these new data regarding the potential harms must be carefully weighed against the risk of not performing a specific medical procedure,” Janet Woodcock, MD, director of the agency’s Center for Drug Evaluation and Research said in a statement accompanying the safety announcement.

While some common procedures like hernia repair generally take far less than three hours, open heart procedures can last up to eight hours.

The warning is based on an FDA evaluation of published studies in pregnant animals and young animals. All showed loss of nerve cells in the brain or effects in the animals’ behavior or ability to learn.

In another study published in 2015, Australian researchers looked at results in infants in 28 hospitals seven nations, including the US, who had anesthesia for less than an hour during hernia repair surgery.

The children were assessed two years after the surgery to see if there were adverse neurodevelopmental outcomes.

They found they showed no such signs, but the results were taken as not useful for weighing the risks in longer procedures.

That research group is planning to follow their study group through five years post-surgery.

The full document “FDA review results in new warnings about using general anesthetics and sedation drugs in young children and pregnant women” lists the drugs and has links to studies.

After a review of existing studies, the FDA today sent out a warning that surgery lasting three hours or more poses a threat of brain or other neurological damage in babies, fetuses, and toddlers.

FDA: Surgery on Babies Risks Brain Damage

Despite a large new study from Germany, the debate over which is better, surgery or interventional procedures to treat aortic valve stenosis has yet to be settled.

Reporting today at the American Heart Association’s Scientific Sessions 2016 in New Orleans, LA, Nicholas Werner, MD, and colleagues from Medical Clinic B, Medizinische Klinikum Ludwigshafen Germany offered research on outcomes from heart patients in the German Aortic Valve Registry (GARY).

At first glance, the results appear to favor surgery.

The GARY results showed that patients who had transcatheter aortic valve implantation (TAVI) at 88 centers in Germany had a 3.8% in-hospital death rate versus 2.6 among in-hospital surgical patients and 16.6% at one year after TAVI versus 8.9% one year after surgical replacement.

The unadjusted death rate was higher after TAVI and a significant difference in one-year mortality rate persisted between the two groups even after propensity score analysis.

But the difference could be explained by factors not related entirely to treatment.

For one thing, the patients who got TAVI may have been too frail for surgery, often due to advanced age. In the GARY study, all were patients with intermediate surgical risk who got isolated interventional or surgical aortic valve replacement (SAVR) for severe symptomatic aortic valve stenosis.

Of 5,997 patients in the study 4,101 had TAVI and 1,896 had SAVR.

“The patients who had TAVI were older, more were female, and were at higher risk of myocardial infarction,” Werner said at a news conference this morning.

Physician judgment over which procedure to use also may have been a confounding factor, as could the fact that some centers’ heart teams were more experienced and simply better at doing their procedures.

“It is not possible to adjust for medical opinion,” Werner said.

Commenting on the study, Craig Smith, MD, of New York Hospital/Columbia, an investigator in the PARTNER II studies on the same issue (the study found TAVI was non-inferior to SAVR) said while the jury is still out on the question of which is better, the latest data from NY State’s registry of heart procedures’ results shows “a two- to three-fold higher risk for surgery.”

He agreed that a lot depended on the where the patient was treated and the skill of the physicians.

Smith commended the investigators on getting “real world” results vs. findings from randomly controlled trials of selected populations’ results after procedures usually done at specialty centers.

An analysis of thousands of patients in Germany taken from a national registry found interventional procedures more dangerous than surgery for severe symptomatic aortic valve stenosis. But there may have been confounding factors.

Real-World Study on Valve Replacement Finds It More Dangerous than Surgery

Deeming Xaracoll to be a drug/device combination, thus requiring a more extensive application, the US Food and Drug Administration (FDA) notified Irish company Innocoll yesterday that it would not be going forward with the New Drug Application as they had filed it for the product in October.

Xaracoll is described as a “bioresorbable bupivacaine-collagen matrix” meant to be inserted into an incision following hernia surgery. Bupivacaine is a local anesthetic, and the purpose of the treatment is to provide quick on-site pain relief following operations. The company believes such an approach could be useful in lowering the opiate burden following the common procedure.

Phase 3 results were announced in May, Innocoll was hoping to have the product to market sometime in 2017, a hope that seems less likely following the FDA’s decision. In the initial announcement, Harold S. Minkowitz, MD, Department of Anesthesiology, Memorial Hermann Memorial City Medical Center, Houston, TX said the treatment “could become an important option for the surgical and anesthesia communities in addressing patient satisfaction with pain management options and the need for opioid-sparing approaches to pain reduction.” 

Those phase 3 trials, MATRIX 1 and 2, used sum of pain intensity over 24 hours as a primary endpoint, with the same metric over 48 and 72 hours as secondary endpoints. Implanted immediately following open laparotomy hernioplasty with mesh as a 300mg dose with a background 650mg of acetaminophen, it met the primary endpoint in MATRIX 1 (p=0.0004) and MATRIX 2 (p<0.0001). MATRIX 2 achieved statistical significance at 48 hours, with MATRIX 1 trending that direction. Both showed decreases in total opiate consumption following surgery and increases in time to first opioid use.

The Refusal to File seems to be more a matter of classification than an outright rejection of the implant’s premise, but remains a setback to Innocoll nonetheless. The company saw its stock prices fall significantly in the immediate aftermath.

Hernias and their subsequent surgical repairs are extremely common. According to the FDA, over a million such operations are performed each year in the US, with mesh-based repairs accounting for more than 90% of groin hernia surgeries. Opioids are commonly prescribed following such surgeries, and, according to some studies, are prescribed overly and unnecessarily. A large University of Pennsylvania study published in JAMA in March found that over 75% of those in their cohort recovering from inguinal hernia repair filled a prescription for the powerful painkillers within a week of the surgery, which the authors characterized as “low-risk.”

The FDA’s Refusal to File was announced last evening by Innocoll in a press release. The company’s CEO Tony Zook said they planned to “work with the FDA over the coming weeks in an effort to address the open issues and to define a path forward for a successful re-filing of our application at the earliest point in time.”

Deeming Xaracoll to be a drug/device combination, the Food and Drug Administration notified Innocoll yesterday that it would not be going forward with the New Drug Application they had filed for the product in October.


October 2016