Pharmacology

IV Anesthesia and Propofol History

The 2018 Lasker-DeBakey Clinical Medical Research Award has been awarded to John B. (Iain) Glen, a veterinarian, for the discovery and development of propofol, our go-to anesthetic induction agent. More unsavoury history recently related to its abuse in anesthesia residents (or in Michael Jackson’s death), as well as it’s appalling adoption for executions. A brief and fascinating history from JAMA

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Nicotine Replacement in Hospitalized Coronary Patients

Some concern exists as to the cardiac safety of using nicotine replacement patches in cardiac disease. The majority of studies indicate it safe to use in stable disease but this observational study is reassuring in finding: “Among smokers hospitalized for treatment of coronary heart disease, use of nicotine replacement therapy was not associated with any differences in short‐term outcomes”.

Outcomes included inpatient mortality, hospital length of stay, and one-month readmission.

These patients had a high degree of cardiac acuity but the authors caution that, due to the known cardiovascular effects of nicotine, randomized along with longer term studies are needed to confirm these reassuring findings in tackling smoking cessation at an early stage of hospitalization.

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Sugammadex Effectiveness in Elderly

Sugammadex was tested tested in elderly patients for reversing deep Rocuronium induced neuromuscular block. Increasingly seen as s faster and more complete agent compared to Neostigmine, this study found that low (as well as common clinical doses) were not as fast or effective in the elderly, and residual blockade and recurarization were more common. Renal function and obesity were risk factors also. The study highlights the need again for universal neuromuscular monitoring in all patients, even when Sugammadex is used.

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Diclofenac cardiovascular risks

All NSAIDs have been linked to increased cardiac risks but this BMJ review singles next out Diclofenac (eg. Voltaren) as the worst agent. “The incidence rate ratio of major adverse cardiovascular events at 30 days among diclofenac initiators increased by 50% versus non-initiators, by 20% versus ibuprofen or paracetamol initiators, and by 30% versus naproxen initiator”.

Adverse events included atrial fibrillation or flutter, ischaemic stroke, heart failure, myocardial infarction, and cardiac death; both sexes of all ages; and even at low doses of diclofenac.

Risk of upper gastrointestinal bleeding at 30 days with diclofenac was similar to that of naproxen, but much higher than for no NSAID initiation, paracetamol, and ibuprofen.

Encountering such patients in the pre-admission setting is an opportunity for counselling and risk mitigation.

Peripheral nerve blockade in diabetic neuropathy

This study found that after ultrasound‐guided popliteal sciatic nerve block, patients with diabetic peripheral neuropathy had a reduced time to onset of sensory blockade, with increased time to first opioid request when compared with patients without neuropathy. 30 ml 1:1 mixture of lidocaine 1% and bupivacaine 0.5% was used

Concern has existed that patients with peripheral neuropathy have increased sensitivity as well as nerve injury risk from local anesthetics. The “double crush” hypothesis of already ischemic/hypoxia nerves suffering more injury from needles or local anesthesia has been a concern although not totally proven; this study was not powered to make such a conclusion. However, it may guide dose selection for peripheral nerve blocks in this population.

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Adverse side effects of dexamethasone in surgical patients

A single dose of Dexamethasone is widely used in anesthesia as an anti-emetic. This Cochrane review sought to assess the effects of a steroid load of dexamethasone on postoperative systemic or wound infection, delayed wound healing, and blood glucose change in adult surgical patients.

They found a single dose of Dexamethasone did not increase infection within 30 days. The data was inconclusive on wound healing, and there was some increase in blood sugar. They caution on extrapolating such data where infection and wound healing may be more likely, such as diabetes or immunodeficiency. Also the surgeries were very heterogeneous, including cardiac, abdominal, neurosurgery, orthopedic etc. and no differentiation is mentioned between elective and emergency surgery. Further studies are awaited.

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Lidocaine for Anesthesia-Related Cough

While Lidocaine has been demoted in ACLS and cardiology, it has enjoyed a renaissance in Anesthesia and Pain Medicine. Intravenous bolus and infusion are being used in opioid-sparing anesthesia and to speed recovery of bowel function and provide analgesia ( link ).

This meta-analysis and review may provide another rationale for its use in anesthesia. Some caution is in order especially for those at risk of cardiac or systemic toxicity, as reports of adverse effects are sparse. It is important to co-ordinate with the surgeon to guard against concurrent local anesthesia infiltration or epidural/nerve blocks that could risk such toxicity.

‘The conclusion: Within a range of 0.5–2 mg·kg−1, intravenous lidocaine dose-dependently prevents intubation-, extubation-, and opioid-induced cough in adults and children with NNTs ranging from 8 to 3. The risk of harm in high-risk patients remains unknown.

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Prothrombin Complex Concentrates For Vitamin K Antagonist Reversal

The following figures emerge from this Anesthesiology review: Annual rates of major hemorrhagic events ranged from 1.0 to 7.4% in a systematic review of patients with atrial fibrillation receiving vitamin K antagonist therapy, while rates of intracranial hemorrhage in the same population ranged from 0.1 to 2.5%. Major bleeding occurred in 3.3% of warfarin-treated patients undergoing elective surgery, but 21.6% in patients in emergency surgery

Fresh Frozen Plasma brings risks of fluid overload, lung injury, infection and is slow to act and less effective. Vitamin K alone is feasible only when surgery can be delayed 24-48 hours.

Current guidelines recommend prothrombin complex concentrates (PCC), specifically four-factor prothrombin complex concentrates, with concomitant intravenous vitamin K, as the preferred therapy for urgent vitamin K antagonist reversal, which are effective in 30 minutes or so. PCCs reduces bleeding and some studies suggest mortality also. Many studies show them to be more effective than FVIIa. Thromboembolism has not been found to be increased to date.

Whereas specific reversal agents are in use or being introduced for Factor Xa Inhibitors and Direct Thrombin Inhibitors, PCCs may be worth considering for hemorrhage in such patients in the interim although their efficacy is very variable for non-vitamin K antagonist reversal.

The full review surveys all the published studies and also examines evidence in various scenarios such as intracranial hemorrhage, cardiac surgery and trauma.

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Midazolam and Dexmedetomidine in Cancer

This is a preclinical study whose clinical significance remains to be determined but illustrates the potential wide ranging effects of medications in the cancer patient.

The study in Anesthesiology found “Midazolam possesses antitumorigenic properties partly mediated by the peripheral benzodiazepine receptor, whereas dexmedetomidine promotes cancer cell survival through signaling via the α2-adrenoceptor in lung carcinoma and neuroglioma cells”.

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Neostigmine-Induced Muscle Weakness

While an immense amount of literature on inadequate neuromuscular block reversal exists, this study shows that Neostigmine in the absence of any neuromuscular block can cause weakness itself, resembling a Phase 1 depolarizing block that may not be readily apparent by train-of-four stimulation.

The clinical scenario may be slightly different in the presence of some residual muscle paralysis but the study speaks to the need for universal (and better) neuromuscular monitors as always, especially if hours have elapsed since a muscle relaxant was given. It will be seized upon by Sugammadex enthusiasts who see this latter agent as a better and quicker reversing agent.

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