Megan Rech

New Drugs of Abuse

Drug abuse is a common problem and growing concern in the United States, and over the past decade, novel or atypical drugs have emerged and have become increasingly popular. Recognition and treatment of new drugs of abuse pose many challenges for health care providers due to lack of quantitative reporting and routine surveillance, and the difficulty of detection in routine blood and urine analyses. Furthermore, street manufacturers are able to rapidly adapt and develop new synthetic isolates of older drugs as soon as law enforcement agencies render them illegal. In this article, we describe the clinical and adverse effects and purported pharmacology of several new classes of drugs of abuse including synthetic cannabinoids, synthetic cathinones, salvia, desomorphine, and kratom. Because many of these substances can have severe or life‐threatening adverse effects, knowledge of general toxicology is key in recognizing acute intoxication and overdose; however, typical toxidromes (e.g., cholinergic, sympathomimetic, opioid, etc.) are not precipitated by many of these agents. Medical management of patients who abuse or overdose on these drugs largely consists of supportive care, although naloxone may be used as an antidote for desomorphine overdose. Symptoms of aggression and psychosis may be treated with sedation (benzodiazepines, propofol) and antipsychotics (haloperidol or atypical agents such as quetiapine or ziprasidone). Other facets of management to consider include treatment for withdrawal or addiction, nutrition support, and potential for transmission of infectious diseases.

When to Pick the Nose: Out-of-Hospital and Emergency Department Intranasal Administration of Medications

&NA; The intranasal route for medication administration is increasingly popular in the emergency department and out‐of‐hospital setting because such administration is simple and fast, and can be used for patients without intravenous access and in situations in which obtaining an intravenous line is difficult or time intensive (eg, for patients who are seizing or combative). Several small studies (mostly pediatric) have shown midazolam to be effective for procedural sedation, anxiolysis, and seizures. Intranasal fentanyl demonstrates both safety and efficacy for the management of acute pain. The intranasal route appears to be an effective alternative for naloxone in opioid overdose. The literature is less clear on roles for intranasal ketamine and dexmedetomidine.

Overview of extended release tacrolimus in solid organ transplantation

Tacrolimus (Prograf(©), Astellas Pharma Europe Ltd, Staines, United Kingdom; referred to as tacrolimus-BID) is an immunosuppressive agent to prevent and treat allograft rejection in kidney transplant recipients in combination with mycophenolate mofetil, corticosteroids, with or without basiliximab induction. The drug has also been studied in liver, heart and lung transplant; however, these are currently off-label indications. An extended release tacrolimus formulation (Advagraf(©), Astagraf XL(©)) allows for once-daily dosing, with the potential to improve adherence. Extended release tacrolimus has similar absorption, distribution, metabolism and excretion to tacrolimus-BID. Phase I pharmacokinetic trials comparing extended release tacrolimus and tacrolimus-BID have demonstrated a decreased maximum concentration (Cmax) and delayed time to maximum concentration (tmax) with the extended release formulation; however, AUC0-24 was comparable between formulations. Overall extended release tacrolimus has a very similar safety and efficacy profile to tacrolimus-BID. It is not recommended in the use of liver transplant patients due to the increased risk of mortality in female recipients. There has been minimal data regarding the use of extended release tacrolimus in heart and lung transplant recipients. With the current data available for all organ groups the extended release tacrolimus should be dosed in a 1:1 fashion, the exception may be the cystic fibrosis population where their initial dose may need to be higher.

Prothrombin Complex Concentrate for Intracerebral Hemorrhage Secondary to Vitamin K Deficiency Bleeding in a 6-Week-Old Child

Four-factor prothrombin complex concentrate is approved for use of life-threatening bleeding secondary to vitamin K antagonism in adults. We describe the use of four-factor prothrombin complex concentrate for hemostasis in a 6-week-old child with life-threatening vitamin K dependent-bleeding who never received vitamin K prophylaxis at birth.

Comparison of Automated Methods Versus the American Burn Association Sepsis Definition to Identify Sepsis and Sepsis With Organ Dysfunction/Septic Shock in Burn-Injured Adults

To develop an algorithm to identify sepsis and sepsis with organ dysfunction/septic shock in burn-injured patients incorporating criteria from the American Burn Association sepsis definition that possesses good test characteristics compared with International Classification of Diseases, Ninth Revision-Clinical Modification (ICD-9) codes and an algorithm previously validated in nonburn-injured septic patients (Martin et al method). This was a retrospective cohort study of consecutive patients admitted to the burn intensive care unit between January 2008 and March 2015. Of the 4761 admitted, 8.6% (n = 407) met inclusion criteria, of which the case rate for sepsis was 34.2% (n = 139; n = 48 sepsis; n = 91 sepsis with organ dysfunction/septic shock). For sepsis identification, the novel algorithm had an accuracy of 86.0% (95% CI: 82.2–89.2%), sensitivity of 66.9% (95% CI: 59.1–74.7%), and specificity of 95.9% (95% CI: 93.5–98.3%). The novel algorithm had better discrimination (0.81, 95% CI: 0.77–0.86) than the ICD-9 method (0.77, 95% CI: 0.73–0.81), although this was not significant (P = .08). For sepsis with organ dysfunction/septic shock, the novel algorithm plus vasopressors (0.67, 95% CI: 0.63–0.72) and the ICD-9 method (0.63, 95% CI: 0.58–0.68) performed equivocal (P = 0.15) but the Martin method (0.76, 95% CI: 0.71–0.81) had superior discrimination than other methods (P < .01). The novel algorithm is an accurate and simple tool to identify sepsis in the burn cohort with good sensitivity and specificity and equivocal discriminative ability to ICD-9 coding. The Martin method had superior discriminative ability for identifying sepsis with organ dysfunction/septic shock in burn-injured patients than either the novel algorithm plus vasopressors or ICD-9 coding.

Pharmacist Participation in Acute Ischemic Stroke Decreases Door-to-Needle Time to Recombinant Tissue Plasminogen Activator

Background: Pharmacists are an important member of the stroke team and aid in obtaining medication and medical history, providing education, managing blood pressure, reviewing exclusion criteria for recombinant tissue plasminogen activator (rtPA), and facilitating reconstitution and administration of rtPA. Objective: To determine if pharmacist presence at bedside during acute ischemic stroke resulted in a reduction in door-to-needle (DTN) times. Methods: This was a retrospective cohort study between January 1, 2011 and December 31, 2015 of patients who received rtPA for acute ischemic stroke in either the emergency department or hospital. Results: Of the 125 included patients, 45 patients (36%) had a pharmacist present (PharmD group) and 80 patients (64%) did not (no PharmD group). Median DTN time was significantly shorter in the PharmD group: 48 minutes versus 73 minutes in the no PharmD group (P < 0.01). The goal of DTN ≤60 minutes was met in 71% of patients in the PharmD group compared to 29% (P < 0.01). Pharmacist at the bedside was the only factor found to be independently associated with reduction DTN time (βcoefficient −23.5 minutes, 95% confidence interval [95% CI] −38.6 to −8.50 minutes). Conclusion: A pharmacist at the bedside of emergency department or in-patient stroke codes reduced DTN time by a median of 23.5 minutes after adjusting for confounding factors and increased the percentage of patients meeting DTN goal time of ≤60 minutes by 49%. These findings support the inclusion of a stroke-competent pharmacist in the bedside response team for acute ischemic stroke patients.

Major publications in the critical care pharmacotherapy literature in 2015

Purpose. Recently published practice guidelines and research reports on pharmacotherapy in critical care patient populations are summarized. Summary. The Critical Care Pharmacotherapy Literature Update (CCPLU) Group is composed of over 50 experienced critical care pharmacists who evaluate 31 peer‐reviewed journals monthly to identify literature pertaining to pharmacotherapy in critical care populations. Articles are chosen for summarization in a monthly CCPLU Group publication on the basis of applicability and relevance to clinical practice and strength of study design. From January to December 2015, a total of 121 articles were summarized; of these, 3 articles presenting clinical practice guidelines and 12 articles presenting original research findings were objectively selected for inclusion in this review based on their potential to change or reinforce current evidence‐based practice. The reviewed guidelines address the management of intracranial hemorrhage (ICH), adult advanced cardiac life support (ACLS) and post‐cardiac arrest care, and the management of supraventricular tachycardia (SVT). The reviewed research reports address topics such as nutrition in critically ill adults, administration of β‐lactams for severe sepsis, anticoagulant selection in the context of continuous renal replacement therapy, early goal‐directed therapy in septic shock, magnesium use for neuroprotection in acute stroke, and progesterone use in patients with traumatic brain injury. Conclusion. Important recent additions to the critical care pharmacy literature include updated joint clinical practice guidelines on the management of spontaneous ICH, ACLS, and SVT.

Risk factors for mortality in septic patients who received etomidate.

PURPOSE To characterize risk factors for mortality in septic patients who received etomidate for rapid sequence intubation. MATERIALS AND METHODS This study was a retrospective cohort conducted at a large, tertiary, urban, academic medical center that included patients with severe sepsis or septic shock who received etomidate between January 1, 2010, and December 31, 2012. RESULTS A total of 169 patients were included with similar baseline characteristics. There were more men in the nonsurvivor group than in the survivor group (67.1% vs 50.6%, P=.03). Septic shock occurred in 91.5% of nonsurvivors and 69% of survivors (P<.01). Nonsurvivors also had a higher initial lactate of (5.1±4.3 mmol/L vs 3.6±3.4 mmol/L, P=.02) and more vasopressor therapy (91.5% vs 69%, P<.01), required a higher number of vasopressors (2.2±1.1 vs 1.3±1, P<.01), and were administered hydrocortisone (53.7% vs 34.5%, P=.01). Abdominal source of sepsis (P=.048) and number of vasopressors (P=.01) were predictive of 30-day mortality. CONCLUSION An alternative sedative induction agent may be considered for use in rapid sequence intubation in patients on multiple vasopressors or with abdominal source of infection.

Intravenous lidocaine for acute pain: a systematic review

This systematic review evaluates the safety and efficacy of intravenous (IV) lidocaine for the treatment of acute pain in adult patients. The PubMed database was searched for randomized controlled trials, retrospective cohort studies, case series, and case reports evaluating the use of IV lidocaine for the treatment of acute pain in adult patients, published between January 1970 and January 2018. The primary outcome was pain reduction via the Visual Analog Scale, Verbal Rating Scale, or Numeric Rating Scale among patients treated with IV lidocaine and placebo or active controls. Safety outcomes included both nonserious and serious adverse events. A total of 347 titles and abstracts were screened, and after full‐text review, 13 studies met the inclusion criteria involving 512 patients. The four active controls studied were IV morphine, IV ketorolac, IV dihydroergotamine (DHE), and IV chlorpromazine (CPZ). The dosing of IV lidocaine varied among studies between a weight‐based dose of a 1‐ to 2‐mg/kg bolus, a fixed‐bolus dose of 50–100 mg, and a 1‐mg/kg/hour continuous infusion. Monitoring of serum lidocaine concentrations was not done routinely. Intravenous lidocaine had superior efficacy to morphine for renal colic and critical limb ischemia, superior efficacy to DHE for acute migraine, and equivalent efficacy to ketorolac for acute radicular lower back pain. However, lidocaine was less effective than CPZ for the treatment of acute migraine. The most common adverse event reported among all studies were neurologic effects such as altered mental status and slurred speech. Due to the inconsistency in dosing, length of administration, and lack of serum monitoring, the absolute safety of IV lidocaine for acute pain is unknown. Larger, prospective studies are needed before the routine use of IV lidocaine can be recommended for all types of acute pain.

Early Recognition and Treatment of Sepsis After the Addition of Lactate to the Laboratory's Critical Result Call List.

Purpose: Screening of patients with sepsis is needed to increase recognition and allow for earlier interventions. There is no consensus on whether the addition of lactate to the critical result laboratory’s call list should be a standard practice. Materials and Methods: This was a retrospective cohort study that compared management and outcomes of patients with sepsis having lactate ≥4 mmol/L before (group 1) and after (group 2) the addition of a critical result threshold of lactate of ≥4 mmol/L to the critical result laboratory’s call list and its effects on time to antibiotics and intravenous fluids (IVFs). Results: One hundred twenty-one patients were included. Lactate was higher in group 1 (7.0 ± 4.3 vs 5.6 ± 2.0, P = 0.03). More patients in group 2 received hydrocortisone (1.9% vs 22.4%, P = .001). Hospital mortality, 30-day mortality, and 90-day mortality were significantly lower in group 2 (59.3% vs 32.8%, P = .003; 68.5% vs 37.3%, P ≤ .001; 68.5% vs 41.8%, P = .002). There were no significant differences in total volume of IVFs (2400.8 ± 1720.0 vs 2483.7 ± 2155.7, P = 0.83), time to start IVFs (184.0 ± 283.2 vs 115.6 ± 190.5, P = 0.27), or antibiotics (184.8 ± 187.1 vs 133.7 ± 137.4, P = 0.16). Conclusion: Addition of lactate to the critical result laboratory’s call list did not lead to a statistically significant improvement in time to IVFs or antibiotics, although the average time to antibiotics and IVFs decreased by 51.1 and 68.4 minutes, respectively. Hospital mortality, 30-day mortality, and 90-day mortality were lower in group 2, which may be, in part, due to increased recognition of severe sepsis by critical result notification and earlier intervention.