Pharmacology

Perioperative management of direct oral anticoagulants (DOACS) in cardiac surgery

An international consensus on managing new oral anticoagulants in patients having cardiac surgery provides pertinent information that will enlighten their use outside cardiac surgery also.

Measurement of DOACS may be useful in emergencies or uncertainty, or in significant renal or hepatic dysfunction; however, such measurement as well as routine coagulation testing is not recommended. Greater caution is also needed in the elderly. Dabigatran is particularly dependent on renal function.

Normal prothrombin time or activated partial thromboplastin time results exclude excess levels of dabigatran, rivaroxaban and edoxaban, but not apixaban. Normal thrombin time precludes significant dabigatran plasma levels, and the aPTT shows some correlation here also – for precise measurements, the diluted thrombin time (dTT), the ecarin clotting time or the ecarin chromogenic assay may be used. For the precise measurement of drug concentrations of all FXa inhibitors, chromogenic and calibrated anti‐FXa tests are recommended.

Reversal agents: for dabigatran, idarucizumab is available; for the FXa inhibitors, andexanet alpha has been approved in the US, and ciraparantag is currently under investigation. Ultrafiltration and Hemodialysis are also discussed for Dabigatran, and non-specific approaches of varying efficacy include prothrombin complex concentrate, fibrinogen concentrate, tranexamic acid and/or factor VIIa.

In general, withholding for 2 days is appropriate. For Dabigatran, this may need 3-5 days depending on renal function. Resumption at therapeutic doses is recommended after 2-3 days and after removal of chest drains. (In the non-cardiac surgery setting, resumption may be sooner depending on bleeding risk). Prophylactic doses may be needed sooner after surgery for thromboembolic prophylaxis. Bridging agents are not recommended for interruptions less than 4 days, as increased bleeding without lower thromboembolism is reported. Individualized approaches may be needed based on CHA2DS2‐VASc Score and bleeding risk.

From an anesthesia perspective, neuraxial anesthesia performance should be equated with high bleeding risk and longer interruption may be the preferred – the ASRA provides one such set of guidelines.

full text link

 

 

Sugammadex in the Elderly

A study using low dose Sugammadex (0.4mg/kg) showed that recovery of train-of-four ratios was slower and recurarization was more common in the elderly after Rocuronium neuromuscular blockade. Renal dysfunction and obesity imposed a higher risk; even 4mg/kg may not suffice in some. The bottom line in all elderly patients is that neuromuscular monitoring is just as imperative with Sugammadex as other agents in ensuring adequate reversal.

link

 

Propofol vs. Inhalational Anesthesia

A systematic review and meta-analysis finds that Propofol anesthesia provides better patient satisfaction, pain scores and an especially better nausea and vomiting outcome as compared with inhalational anesthesia, with a marginal increase in time for respiratory recovery and extubation.

While some recent studies have yielded opposing results on the effect of total intravenous anesthesia on cancer recurrence and mortality, there seems ample reason to choose Propofol based anesthesia. Further prospective validating studies are suggested.

link

 

Acute Pain in Buprenorphine-Maintained Patients

Buprenorphine is increasingly encountered as a maintenance agent in substance use disorders rather than Methadone. Analgesia in such patients is challenging due to the complex partial agonist and antagonist properties of this agent.  Strategies include continuing buprenorphine for minor surgeries – often dividing the daily dose, or stopping it before surgery and using other opioids for analgesia in major surgery.

This study found that in those maintained on 12-16mg daily with last dose c. 17 hours ago,  up to 32mg of either IV Hydromorphine or Buprenorphine was effective. “However, the use of hydromorphone for analgesia in buprenorphine-maintained individuals confers greater abuse liability and side effects than does supplemental intravenous buprenorphine”. Analgesia requirement, side effects, drug interactions and factors like whether Buprenorphine is stopped or continued must all be taken into account.

Procedural Sedation

A recent guideline from the American College of Emergency Physicians on unscheduled procedural sedation is interesting to compare with  American Society of Anesthesiologists’ views on sedation. There have been longstanding tensions between the ASA and others who administer sedation such as gastroenterologists and dentists.

The ACEP take the view that the proceduralist can give or direct giving sedation and that the level of responsiveness and ventilation are more important than the agent used (clearing the way for Propofol!). Skills are needed to rescue a patient who slips into deep sedation or general anesthesia.

The risk of gastric aspiration so central to Anesthesia practice is downplayed with reasonable evidence of how rare an occurrence it is, an issue sure to provoke controversy.

link

 

Totally intravenous anesthesia guidelines (TIVA)

Total intravenous anaesthesia is mandatory far malignant hyperthermia, and is also commonly used for airway surgery, anaesthesia outside the operating room and during transport.  It also possesses advantages for those with a history of nausea and vomiting, or allowing measurement of evoked potentials.

These novel consensus guidelines from the UK & Ireland encompass all theoretical and practical aspects, in  particular the use of Propofol and Remifentanil.  They recommend target controlled infusion (not available everywhere). Allowance must be made for the pharmacokinetic models when concomitant agents are used, or in the elderly or sick/frail and obese. Remifentanil infusion has been linked to acute tolerance and opioid induced hyperalgesia.

Suggested doses are given, as well as cautions with pump and tubing setup. Awareness risk is especially important, and where neuromuscular blocking agents are used, processed EEG monitoring is recommended.

The link provides an excellent introduction and overview:

link

 

Debunking Penicillin Allergy

Most patients with a history and label of penicillin “allergy” are found not to be so. “To be on the safe side” avoidance of penicillin and cephalosporins is documented as actually increasing infective risks with suboptimal (often more costly) alternatives – higher surgical site infection and risks of MRSA and C. Difficile. This full text article discusses the issue as well as importantly the approaches to such patients in terms of skin testing and the current trend of oral penicillin challenge.

link

 

Dexmedetomidine and ICU Delirium

The use of anti-psychotics has consistently failed to provide significant improvement in critically ill patients with delirium, as in this study ( link ).

Dexmedetomidine has on the other hand signalled promising effects and this systematic review and meta‐analysis suggests that dexmedetomidine reduces the incidence of delirium and agitation in intensive care patients, evidence ranged from moderate to high.

The incidence of hypotension and bradycardia were also higher, as is common with this agent.

link

 

Pantoprazole for ICU GI Bleeding Prophylaxis

The use of PPIs in critical care for gastrointestinal bleeding prophylaxis has been part of many bundles of ICU care but concerns exist as to side effects like increased nosocomial pneumonia and C. Difficile infection.

This study found “Among adult patients in the ICU who were at risk for gastrointestinal bleeding, mortality at 90 days and the number of clinically important events were similar in those assigned to pantoprazole and those assigned to placebo”.

It may be the more common use of enteral nutrition today lessens the risk. Higher risk groups could still be considered for prophylaxis.

link

NEJM editorial link