Current Practices in Tranexamic Acid Administration for Pediatric Trauma Patients in the United States.

BACKGROUND: Although controversial, early administration of tranexamic acid (TXA) has been shown to reduce mortality in adult patients with major trauma. Tranexamic acid has also been successfully used in elective pediatric surgery, with significant reduction in blood loss and transfusion requirements. There are limited data to guide its use in pediatric trauma patients. We sought to determine the current practices for TXA administration in pediatric trauma patients in the United States. METHODS: A survey was conducted of all the American College of Surgeons-verified Level I and II trauma centers in the United States. The survey data underwent quantitative analysis. RESULTS: Of the 363 Level I and II qualifying centers, we received responses from 220 for an overall response rate of 61%. Eighty of 99 verified pediatric trauma centers responded for a pediatric trauma center response rate of 81%. Of all responding centers, 148 (67%) reported they care for pediatric trauma patients, with an average of 513 pediatric trauma patients annually. The pediatric trauma centers report caring for an average of 650 pediatric trauma patients annually. Of all centers caring for pediatric trauma, 52 (35%) report using TXA, with the most common initial dosing being 15 mg/kg (68%). A follow-up infusion was utilized by 45 (87%) of the programs, most commonly dosed at 2 mg/kg/hr × 8 hr utilized by 24 centers (54%). CONCLUSION: Although the clinical evidence for TXA in pediatric trauma patients is limited, we believe that consideration should be given for use in major trauma with hemodynamic instability or significant risk for ongoing hemorrhage. If available, resuscitation should be guided by thromboelastography to identify candidates who would most benefit from antithrombolytic administration. This represents a low-cost/low-risk and high-yield therapy for pediatric trauma patients.

Consensus Perioperative Management Best Practices for Patients on Transdermal Fentanyl Patches Undergoing Surgery.

PURPOSE OF REVIEW: The administration of a transdermal fentanyl patch can be complicated with different pharmacokinetics than other fentanyl preparations. RECENT FINDINGS: The medical condition and baseline opioid requirements must all be carefully considered when dosing a fentanyl patch. An advantage of the fentanyl patch is its ability to bypass the gastrointestinal tract and in many patients, provide effective analgesia with minimal side effects. Fentanyl patches must be carefully administered since morbidity and/or mortality can result from the following: Giving higher doses than a patient needs, combining the medication with potent sedatives, or heating a fentanyl patch. The use of a transdermal fentanyl patch for the treatment of acute postoperative pain is not recommended and any patient undergoing a surgical procedure should have the fentanyl patch removed preoperatively. The current manuscript discusses the history of fentanyl and the fentanyl patch, as well as perioperative considerations, contraindications, current clinical efficacy, and clinical adversities related to the transdermal fentanyl patch. Regarding the heating of a transdermal fentanyl patch, which significantly increases blood levels of fentanyl, it is of the utmost importance that the patch be removed prior to surgery.

Comprehensive Perioperative Management Considerations in Patients Taking Methadone.

PURPOSE OF REVIEW: Well-informed staff can help decrease risks and common misconceptions regarding opioid-tolerant patients, especially those taking methadone. RECENT FINDINGS: In 2015, opioid pain relievers were the second most used drug at 3.8 million. Overdose death was three times greater in 2015 than in 2000. Medication-assisted treatment was sought by more than 2 million individuals with substance use disorder, one of which is methadone. Chronic pain affects millions of adults in the USA. Opioid therapy is widely used among these adults. Related to the risk of abuse and dependence, guidelines suggest that opioid therapy may not be considered first-line treatment. A multidisciplinary approach, including thorough preoperative evaluation, the utilization of multimodal pain management strategies, and opioid-sparing techniques in both the intraoperative and postoperative periods will allow for the best possible outcome.

Bupropion Mediated Effects on Depression, Attention Deficit Hyperactivity Disorder, and Smoking Cessation.

Bupropion had been in use since the late 1980s as an unconventional treatment for depression. Unlike other antidepressants, bupropion has no serotonergic activity and inhibits the reuptake of norepinephrine and dopamine. The drug has been used to treat depression, Attention Deficit Hyperactivity Disorder (ADHD), and smoking cessation. This investigation reviews the pharmacokinetic and pharmacodynamic effects of bupropion and its mechanisms of action and interactions with other drugs. We evaluated the efficacy of major on and off-label uses of bupropion, focusing on the indications, benefits, and adverse effects. Our review demonstrates that bupropion is superior to placebo and non-inferior to SSRIs such as escitalopram in treating major depressive disorder. More research is needed to determine positive patient-centered outcomes such as increases in quality of life. In the case of ADHD, the evidence for efficacy is mixed with poorly conducted randomized clinical trials, small sample sizes, and a lack of long-term assessments. The same is true in the case of bipolar disorder in which there is still limited and controversial data available on bupropion's safety and efficacy. In the case of smoking cessation, bupropion is found to be an effective anti-smoking drug with synergistic benefits when used as a combination therapy. We conclude that bupropion has the potential to provide benefit for a subset of patients who do not tolerate other typical antidepressants or anti-smoking therapies or for those whose treatment goals align with bupropion's unique side effect profile, such as smokers who wish to quit and lose weight. Additional research is needed to determine the drug's full clinical potential, particularly in the areas of adolescent depression and combination therapy with varenicline or dextromethorphan. Clinicians should use this review to understand the varied uses of the drug and identify the situations and patient populations in which bupropion can lend its greatest benefit.

Lamotrigine and Stevens-Johnson Syndrome Prevention.

Stevens-Johnson Syndrome (SJS) is a rare life-threatening condition characterized by severe mucocutaneous epidermal necrolysis and detachment of the epidermis. The condition centers around a delayed-type hypersensitivity reaction with a complex etiology stemming from a variety of causes. The number one cause is medication-related-common ones including sulfonamides, antiepileptics, allopurinol, and nonsteroidal anti-inflammatory drugs. Genetics also play a role as several human leukocyte antigen (HLA) genotypes within certain ethnic groups have been implicated in adverse reactions to specific drugs. HLAB*15:02 has been identified in the Chinese and others of Southeast Asian origin to increase susceptibility to lamotrigine and carbamazepine-induced SJS. Furthermore, patients of Japanese origin with HLAB*31:01 and Koreans with HLA-B*44:03 are also at increased risk of SJS after receiving the same two drugs. Of the antiepileptics, one most commonly associated with SJS is lamotrigine, a pre-synaptic voltage-gated sodium channel inhibitor. Lamotrigine is an antiepileptic drug of the phenyltriazine class that is indicated for the prevention of focal and generalized seizures in epileptic patients as well as monotherapy or adjunctive maintenance treatment for Bipolar disorder. The occurrence of SJS is not a rigid contraindication to lamotrigine reintroduction in the same patient. To facilitate this, manufacturers have developed a strict re-challenge dosing regimen to facilitate successful reintroduction of lamotrigine. In order to prevent the recurrence of SJS during a re-challenge, timing of re-dose and initial rash severity must be considered. Therefore, to prevent SJS recurrence, prime lamotrigine re-challenge patients are those with mild initial rash that has not occurred within the previous 4 weeks. The Federal Food and Drug Administration recommends the testing HLA subtypes for those associated with SJS prior to starting lamotrigine.

Clinical management of the pregnant patient undergoing non-obstetric surgery: Review of guidelines.

The management principles of non-obstetric surgery during pregnancy are important concepts for all health care providers to be cognizant of. The goals of non-obstetric surgery are to ensure maternal safety, maintain the pregnancy, and ensure fetal well-being. In this regard, organogenesis occurs roughly between days 7-57 and thus, certain medications have a higher incidence of fetal teratogenicity in this first trimester. Some examples of common surgeries performed urgently or emergently include appendectomies, ovarian detorsions, bowel obstruction, trauma, and cholecystectomies. The choice of anesthetic technique and the selection of appropriate anesthetic drugs should be guided by indication for surgery, the nature of the surgery, and the site of the surgical procedure. Many of the concerns for any patients undergoing urgent or emergent surgery must be considered by anesthesia providers along with steps to ensure the fetus has the best outcome.

Chronic pain and substance abuse disorders: Preoperative assessment and optimization strategies.

There is an ever-increasing number of opioid users among chronic pain patients and safely managing them can be challenging for surgeons, anesthesiologists, pain experts, and addiction specialists. Healthcare providers must be familiar with phenomena typical of opioid users and abusers, including tolerance, physical dependence, hyperalgesia, and addiction. Insufficient pain management is very common in these patients. Patient-centered preoperative communication is integral to setting realistic expectations for postoperative pain, developing successful nonopioid analgesic regimens, minimizing opioid consumption during the postoperative period, and decreasing the number of opioid pills at the risk of diversion. Preoperative evaluation should identify comorbidities and identify risk factors for substance abuse and withdrawal. Intraoperative and postoperative strategies can ensure safe and effective pain management and minimize the potential for morbidity and mortality in this high-risk patient population.

Newer nerve blocks in pediatric surgery.

PURPOSE OF THE REVIEW: The purpose of this manuscript is to provide a brief discussion of the current direction in pediatric regional anesthesia, highlighting both newer nerve blocks and techniques and traditional nerve blocks. RECENT FINDINGS: The number of nerve blocks performed in pediatric patients continues to increase. This growth is likely related in part to the recent focus on perioperative multimodal analgesia, in addition to growing data demonstrating safety and efficacy in this patient population. Multiple studies by the Pediatric Regional Anesthesia Network (PRAN) and the French-Language Society of Pediatric Anesthesiologists (ADARPEF) have demonstrated lack of major complications and general overall safety with pediatric nerve blocks. The growing prevalence of ultrasound-guided regional anesthesia has not only improved the safety profile, but also increased the efficacy of both peripheral nerve blocks and perineural catheters. SUMMARY: As the push for multimodal analgesia increases and the breadth of pediatric regional anesthesia continues to expand, further large prospective studies will be needed to demonstrate continued efficacy and overall safety.

Does promethazine shorten the length of stay in the post anesthesia care unit?

The combination of promethazine and opioids is known to have an opioid-sparing effect, thereby facilitating a reduction in total patient opioid consumption. In recent years, this practice has fallen out of favor in many healthcare facilities, except primarily in the post anesthesia care unit (PACU). The goal of this study was to highlight the potential of promethazine as a direct or indirect adjuvant medication in acute pain management. The present investigation was undertaken with a case series of adult female patients who underwent open total abdominal hysterectomies. Data from the PACU was reviewed with patients being separated into two groups. Group 1 received only intravenous opioids for acute pain management. Group 2 received a combination of intravenous opioids for acute pain management and intravenous promethazine for nausea and/or vomiting. Patients were discharged from the PACU with a modified Aldrete score of 9 or 10. The study showed that patients who received promethazine in addition to opioids were discharged from the PACU an average of 19.2 minutes earlier than those patients who received only opioids (p=0.003). The time to achieve modified Aldrete score of 9 or higher was more quickly achieved when open abdominal hysterectomy patients received promethazine in addition to opioids in the PACU. The study concluded that promethazine, in combination with opioids, could potentially decrease PACU stay postoperatively. Based on the present investigation, the prospect of using promethazine in other facets of pain management are intriguing and warrant future studies. Specifically, it may be worth investigating whether promethazine is truly an adjunct in combination with opioids and to determine if there are any other antihistamines or neuroleptics which may have similar clinical effects to promethazine.

New opioid receptor modulators and agonists.

There has been significant research to develop an ideal synthetic opioid. Opioids with variable properties possessing efficacy and with reduced side effects have been synthesized when compared to previously used agents. An opioid modulator is a drug that can produce both agonistic and antagonistic effects by binding to different opioid receptors and therefore cannot be classified as one or the other alone. These compounds can differ in their structures while still possessing opioid-mediated actions. This review will discuss TRV130 receptor modulators and other novel opioid receptor modulators, including Mitragyna "Kratom," Ignavine, Salvinorin-A, DPI-289, UFP-505, LP1, SKF-10,047, Cebranopadol, Naltrexone-14-O-sulfate, and Naloxegol. In summary, the structural elucidation of opioid receptors, allosteric modulation of opioid receptors, new opioid modulators and agonists, the employment of optogenetics, optopharmacology, and next-generation sequencing of opioid receptor genes and related functionality should create exciting new avenues for research and therapeutic development to treat conditions including pain, opioid abuse, and addiction.

Pharmacogenomics, precision medicine, and implications for anesthesia care.

The study of how individual genetic differences, known as polymorphisms, change the pharmacokinetics and pharmacodynamics of drugs is called pharmacogenomics. As the field of pharmacogenetics grows and continues to identify genetic polymorphisms, it is promising that the unmet need in this patient population may soon be addressed with personalized drug therapy based on the patient's genetic composition. Although encouraging, pharmacogenomic testing is underutilized in the United States and is often not covered by insurance companies. This manuscript describes the current state of precision medicine as it relates to perioperative care and how preoperative genomic analysis can help improve patient outcomes. This investigation also outlines future directions in this important and evolving field.