restoring muscle function; (2) the NMBAs that are already bound to nicotinic receptors will dissociate from the receptor (Answer C). Sugammadex exerts its effect by forming very tight complexes at a 1:1 ratio with aminosteroid muscle relaxants (rocuronium > vecuronium >> pancuronium). The intermolecular (van der Waals’) forces, thermodynamic (hydrogen) bonds and hydrophobic interactions make the sugammadex–rocuronium complex very tight. The resulting reduction in free‐rocuronium plasma concentration creates a gradient between the tissue compartment (including the neuromuscular junction) and plasma‐free rocuronium moves from tissue to plasma, with a reduction in nicotinic receptor occupancy at the neuromuscular junction. Multiple trials have found sugammadex is faster at reversing rocuronium‐ and vecuronium‐induced paralysis than both neostigmine and edrophonium (Answer D) while having similar adverse event profiles as the traditional cholinesterase inhibitors. Atropine and glycopyrrolate (Answer A) are both anticholinergic drugs that are often used in conjunction with cholinesterase inhibitors (neostigmine and edrophonium) to help offset their cholinergic effects such as bradycardia and excessive salivation. They have no role in NMBA reversal when used by themselves.Answer: CAbrishami A, Ho J, Wong J, et al. Sugammadex, a selective reversal medication for preventing postoperative residual neuromuscular blockade. The Cochrane Library. 2009 Oct; 7(4):CD007362.Welliver, M, McDonough J, Kalynych N, et al. Discovery, development, and clinical application of sugammadex sodium, a selective relaxant binding agent. Drug Des Devel Ther. 2008; 2 : 49–59.Keating, GM Sugammadex: a review of neuromuscular blockade reversal. Drugs. 2016; 76 (10):1041–1052.21 A 42‐year‐old man with no past medical history was in a motor vehicle crash and sustained a large subdural hematoma. The patient is intubated and taken to the operating room for a decompressive craniotomy. On postoperative day 6 while still intubated, the patient develops thick purulent‐looking secretions, has a WBC 13 000, and a fever to 38.4°C. Blood cultures, urine cultures, and bronchial alveolar lavage are obtained. What should be the empiric therapy for his suspected ventilator‐associated pneumonia?Vancomycin and ciprofloxacinVancomycin and gentamicinVancomycin and cefepimeCeftriaxone and azithromycinAmpicillin‐sulbactam and doxycyclinePer 2016 guidelines, antibiotic coverage for ventilator‐associated pneumonia (VAP) should include an active agent against MRSA when risk factors for antimicrobial resistance is present (prior IV antibiotics within 90 days, septic shock at time of VAP, ARDS preceding VAP, 5 or more days of hospitalization prior to VAP, acute renal replacement therapy). This patient most likely received antibiotics prior to his craniotomy and has been in the hospital > 5 days, and therefore needs both MRSA and gram‐negative coverage. This patient does not require double Pseudomonas coverage assuming he is in an intensive care unit that has antimicrobial resistance defined as < 10% of gram‐negative isolates resistant to an agent considered for monotherapy. Fluoroquinolones and aminoglycosides (Answers A & B) should not be used as monotherapy for gram‐negative coverage for ventilator‐associated pneumonia. Answers D and E are both reasonable treatments for community‐acquired pneumonia but are not appropriate for ventilator‐associated pneumonia. In this case, cefepime would be preferred to piperacillin‐tazobactam for gram‐negative coverage as cefepime has CNS penetration and this patient has had neurosurgical intervention.Answer: CKalil AC, Metersky ML, Klompas M,et al. Management of adults with hospital‐acquired and ventilator‐associated pneumonia: 2016 clinical practice guidelines by the Infectious Diseases Society of America and the American Thoracic Society. Clin Infect Dis. 2016; 63 (5): e61–e111.Torres A, Niederman MS, Chastre J, et al. International ERS/ESICM/ESCMID/ALAT guidelines for the management of hospital‐acquired pneumonia and ventilator‐associated pneumonia: guidelines for the management of hospital‐acquired pneumonia (HAP)/ventilator‐associated pneumonia (VAP) of the European Respiratory Society (ERS), European Society of Intensive Care Medicine (ESICM), European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and Asociación Latinoamericana del Tórax (ALAT). Eur Respir J. 2017; 50 (3):1–26. PMID: 28890434.
22 A 33‐year‐old man, otherwise healthy, has acute appendicitis and will be undergoing a laparoscopic appendectomy. He mentions both his father and brother have been diagnosed with malignant hyperthermia. The patient has never had surgery before and has not been tested for the gene. Which is the best plan for anesthesia?Succinylcholine followed by isofluraneSuccinylcholine followed by desfluraneRocuronium followed by sevofluraneRocuronium followed by propofolRocuronium followed by nitrous oxideMalignant hyperthermia is a rare autosomal dominant disorder which is characterized by skeletal muscle hypermetabolism following exposure to halogenated anesthetics, succinylcholine, or rarely, physiologic stress. The mutation is often found on the RYR1 gene. Exposure to halogenated gasses or succinylcholine causes uncontrolled release of calcium from the sarcoplasmic reticulum leading to sustained muscle contraction. Signs and symptoms are tachycardia, tachypnea, hypoxemia, hypercarbia, metabolic acidosis, hyperkalemia, cardiac dysrhythmias, hypotension, skeletal muscle rigidity, and hyperthermia. Earliest signs are often hypercarbia and tachypnea followed by hyperthermia. Treatment is to stop the inciting agent, call for help, administer dantrolene 2.5 mg/kg until the reaction subsides, increase tidal volume, start aggressive cooling measures, treat arrythmias (avoid calcium channel blockers), check electrolytes, and continue dantrolene 1 mg/kg every 4 hours for 24 to 48 hours. The gold standard test is the caffeine halothane contracture test. As this requires a muscle biopsy, genetic testing is becoming more common.Succinylcholine and the halogenated gasses (isoflurane, desflurane, and sevoflurane) are known triggers for malignant hyperthermia, and should be avoided in this patient (Answers A, B, C). While nitrous oxide (Answer E) is not a halogenated gas, it is not typically used with laparoscopic surgeries as there is concern for bowel distension.Answer: DWatt S, McAllister RK . Malignant Hyperthermia. Stat Pearls Publishing . 2020Ruffert H, Bastian B, Bendixen D, et al. Consensus guidelines on perioperative management of malignant hyperthermia suspected or susceptible patients from the European Malignant Hyperthermia group. Br J Anaesth. 2021; 126(1):120–130. doi: https://doi.org/10.1016/j.bja.2020.09.029. Epub 2020 Oct 31. PMID: 33131754
11 Transfusion, Hemostasis, and Coagulation
Lindsey Karavites, MD and Kazuhide Matsushima, MD
Division of Acute Care Surgery, University of Southern California, LAC+USC Medical Center, Los Angeles, CA, USA
1 57‐year‐old man was brought into the trauma bay after a witnessed fall from his third‐floor apartment onto the sidewalk. He is lethargic but arousable with blood pressure 80/40 mmHg and heart rate 135 beats/min. He is noted to have a scalp laceration and bilateral lower extremity deformities with significant blood loss noted at the scene. What is one advantage of selecting low titer whole blood for his resuscitation over component therapy?24‐hour survival benefit in the severely injured.Decreased 24‐hour total transfusion requirement.Cost effectiveness of prolonged time to product expiration.Decreased transfusion reactions due to standardized safe antibody titer levels.No risk of post‐transfusion hemolysis.Increasing retrospective data from the military medical community for use of whole blood in resuscitation have led to similar efforts in civilian trauma patients. Low titer whole blood may have institution specific definitions; however, it is generally considered unseparated blood collected from a donor with low titers of Ig M and/or IgG anti‐A and anti‐B. Implementation of cold‐stored low‐titer anti‐A and anti‐B group O whole blood (LTOWB) transfusion strategies are in place in civilian trauma centers but further prospective data are necessary to examine discrete comparisons of whole blood without simultaneous use of components, verification of appropriate safety, and determination of cost–benefit analyses. To date, the only randomized controlled pilot trial comparing the use of whole blood to component therapy demonstrated that those receiving whole blood required fewer blood products at 24 hours with no difference in mortality. Another recent study comparing between LTOWB vs. component therapy showed that the use of LTOWB was significantly associated with a reduction in post‐emergency department blood transfusion and improved 30‐day survival. Additional advantages include ease of use with single bag product storage, reduced human error with administration, decreased transfusion reactions, although no standard safe antibody titer levels
