You've intubated. Now what?

Congratulations — tube in, RSI complete, and CXR/EtCO2/physical exam confirm placement. What now? How will you manage her meds on the vent? Infusion? Pushes?

Consider the patient's age, weight, drug/alcohol use, comorbidities, and renal/hepatic functions.

1. Pick analgesia. Give a bolus and make sure it's adequate, then start an infusion

2. Pick sedation if necessary, but be wary

What did she actually receive? Fentanyl and propofol. Was this a good choice for her?

Her Outcome

When I arrived on the unit the next AM, her lactic acid was 7.9. I noticed HR was decreasing: she was 110-120 on arrival but was now in the 40s-50s. Not good!

Looking over her medications, vent settings, volume status, and overall clinical course, it was decided that the propofol should be switched to Versed.

Lactic acid improved!

What did she have?

Propofol Infusion Syndrome (PIS)

Defined as metabolic acidosis with cardiac dysfunction and one or more of the following: rhabdomyolysis, hypertriglyceridemia, or renal failure.

However, intralipid propofol may impair hepatic lactate metabolism leading to lactate accumulation and acidosis.

The disease commonly presents as an otherwise unexplained high anion gap metabolic acidosis, rhabdomyolysis, hyperkalemia, acute kidney injury, elevated liver enzymes, and cardiac dysfunction. Management of overt propofol infusion syndrome requires immediate discontinuation of propofol infusion and supportive management, including hemodialysis, hemodynamic support, and ECMO in refractory cases.

For Sedatives

Current practice favors intermittent bolus doses, daily interruption or dose minimization titrated to light level of sedation (RASS -2 to 0) of continuous infusions [3]. Clinical practice guidelines for the sustained use of sedatives and analgesics in critically ill adults endorse the initial use of intermittent bolus dose, with the initiation of continuous infusions with daily interruption or dose minimization titrated to light level of sedation in patients who require intermittent infusions more often than every two hours [7].

Early Interventions Matter (ED)

• The SPICE trial: deep early sedation within the first four hours was an independent predictor for delayed extubation and increased mortality. (Shehabi 2012)

• If you don’t give enough analgesic, you’ll end up unnecessarily giving more sedation

• Increase in RASS scores, systolic, and diastolic blood pressure in mechanically ventilated patients receiving sedation only when compared to patients also receiving analgesia (Jeitziner 2012)”

• Not all mechanically ventilated patients require sedatives.

• A randomized controlled trial of 140 patients: patients in the solo analgesia group had statistically significantly more days without mechanical ventilation and on average shorter ICU length of stays. (Strom 2010)

• Use of succinylcholine compared to longer acting NM blocking agents for RSI associated with higher likelihood of post RSI sedation. (Lembersky 2019)

Analgesic: Opioids

• CNS and peripheral tissue

  • Mu- 1 receptor binding: analgesia

  • Mu-2 receptors: respiratory depression, vomiting, constipation, and euphoria

  • Kappa receptor: sedation, miosis, and spinal analgesia

• Provide mild anxiolysis, but no amnesia

• PROS:

  • Good for dyspneic and suppresses cough reflex

  • Little cardiovascular effect in euvolemic patients

• CONS:

  • In hypovolemic patients with reduced cardiac output, decreased venous return, reduced sympathetic tone, and reduction in heart rate can result in hypotension

  • Synergistic effect on hemodynamics (ie. hypotension) and sedation when coupled with benzos

Analgesic/Sedative: Ketamine

• MOA: NMDA receptor antagonist, phencyclidine derivative

• Analgesic and sedative

• PROS:

  • Great for the status asthmaticus (relaxes bronchial smooth muscle)

  • Great for the hypotensive patient

• CONS:

  • Contraindicated in hypertension, cardiovascular disease, high intracranial pressure (controversial), preeclampsia, glaucoma, seizure (lower seizure threshold) and history of psychosis (altered mood/delirium), laryngospasm

Analgesic/Sedative: Dexmedetomidine

• MOA: central α2 agonist similar to clonidine, but more specific

• Analgesia and sedation

• Lipophilic

• PROS:

  • Provides sedation and analgesic without respiratory depression

  • Provides lighter sedation, great for delirium and best to use when attempted to extubate

• CONS:

  • Bradycardia and hypotension if titrated too quickly

  • Extensive hepatic metabolism

Sedative: Benzos

• MOA: g-aminobutyric acid (GABA) receptor CNS blockade

• Anxiolytic with sedative and hypnotic effects at increasing doses

• PROS:

  • Antiepileptic

  • Subtle drug-drug interaction because of above

• CONS:

  • Propylene glycol toxicity with some

  • Some data suggesting worse outcomes with benzos compared to propofol or dexmedetomidine: delirium, oversedation, delayed extinction and longer time to discharge

  • Have to be mindful in patients with hepatic and renal dysfunction

Sedative: Propofol

• MOA: Unclear mechanism; GABAergic effects on CNS

• Lipophilic: onset in seconds/minutes with redistribution to peripheral tissues and a large volume of distribution

• Powerful anxiolytic and amnestic

• PROS:

  • Antiepileptic

  • Allows for serial neurologic assessments due to rapidity of action, ease of titration, and lack of active metabolites

  • Preferred in TBI as may decrease cerebral oxygen consumption and reduce ICP

• CONS:

  • Can cause hypotension, particularly in under-volume-resuscitated patients

  • Lactic acidosis, hypertriglyceridemia, propofol infusion syndrome

Opioids and Anesthetics

Opioids are successfully used in patients with liver diseases, and Fentanyl is the drug of choice for these patients. As the average dosage of drug is used, oxygen content of the liver and liver blood flow are not affected [14, 16].

Among the drugs used for induction of anesthesia, propofol is the drug of choice in patients with liver diseases [17]. As a rule, any type of long-acting local anesthetic in patients with cirrhosis should be avoided. Fentanyl from narcotics, lorazepam and oxazepam from sedatives, along with some volatile anesthetic agent such as Sevoflurane or intravenous anesthetics such as propofol are recommended in these patients [18-20].

Benzos

The ‘LOT’ drugs are those metabolized mostly by conjugation:

• L – Lorazepam

• O – Oxazepam

• T – Temazepam

These do not have active metabolites, and the half-life remains relatively the same even in the setting of liver disease.

The rest of the benzodiazepines are primarily metabolized via hepatic CYP-mediated oxidation. These may have prolonged duration of effect in patients with marked liver impairment, particularly the drugs with active metabolites such as diazepam, clonazepam, and midazolam. Some practitioners like to take advantage of the longer duration of action and active metabolites. Others prefer to have more predictable kinetics in patients with liver disease and stick with the ‘LOT’ options.

• Go hard on those opioids

• Add a pressor

• Sedation in patients with severe RD shows poorer outcomes

• Midazolam has delayed metabolism/elimination in renal impairment and should be avoided

• Dexmedetomidine has been used and is effective