Airway management is a detail-oriented sport. Minor nuances of patient positioning can be essential. Or gentle laryngeal manipulation. Apneic oxygenation can improve first-pass success. Placing the pulse oximeter on the same arm as the blood pressure cuff can cause real headache. Failure to recognize and remove dentures is an enormous pitfall. An endotracheal tube placed too deep can cause hypoxemia and pneumothorax.
The difference between success and failure hinges on details. Optimizing each detail increases the likelihood of success. This post explores what might seem like a trivial detail: the ideal order of administration of rocuronium and ketamine for rapid sequence intubation (RSI).
The question: Rocketamine vs. Keturonium
Let's start with a common scenario. You need to perform RSI on a man with morbid obesity in hypoxemic respiratory failure. Even with perfect preoxygenation, you can't get his oxygen saturation above 96%. What is the best order of administration of medications?
- (a) Push rocuronium, then push ketamine.
- (b) Push ketamine, then push rocuronium.
Defining time intervals in RSI
The safe apnea time is the amount of time that a patient will tolerate apnea,
before developing critical hypoxemia. For normal people undergoing elective anesthesia, this may be close to ten minutes (blue arrow above). For this patient, the apnea time is probably closer to 2 minutes (yellow arrow above). He is starting off with a saturation of 96%, near the steep portion of the desaturation curve. Given his morbid obesity, he is likely to de-recruit, shunt, and desaturate rapidly.
Sedation lag time
The sedation lag time is the interval in between onset of sedation and when the patient reaches complete paralysis. During the sedation lag time, bad things are happening: the patient's respiratory efforts drop, the lungs start to de-recruit, PaO2 starts falling, and PaCO2 is increasing. A prolonged sedation lag time will cut into the safe apnea time, reducing the time available to perform laryngoscopy.
The entire concept behind rapid sequence intubation is that the sedation lag time should be as short as possible. Ideally, the patient would go directly from breathing deeply (recruiting their lungs and clearing carbon dioxide) to a state of unconscious paralysis (blue curve below).
Using higher doses of rocuronium (e.g. ~1.2-1.4 mg/kg), paralysis typically occurs about 50-90 seconds after injection. Most patients will paralyze by 50-60 seconds, but shock may cause delays due to sluggish circulation of drug into the muscle.
Based on this onset time, it's generally wise to wait at least ~60 seconds after pushing rocuronium before starting laryngoscopy. Before 50-60 seconds, the patient is unlikely to be adequately paralyzed, leading to a risk of vomiting. This has been discussed previously (Pearl #9).
The pharmacokinetics of rocuronium may be roughly represented as follows:
Ketamine has a fairly fast onset of action following a bolus. Most sources suggest an onset time of ~30-40 seconds following IV bolus (1). Notably, a large bolus of ketamine (e.g. 1.5-2 mg/kg) will often cause a short period of complete apnea and unconsciousness. The pharmacokinetics of ketamine may be represented as follows:
Now let's return to our initial question of how to sequence rocuronium and ketamine. It takes about 15 seconds to give the first drug and flush the IV before giving the second drug. This leads to two scenarios.
Rocketamine (Rocuronium then ketamine)
In this scenario, ketamine is pushed second, but it works faster so it still tends to kick in first. Meanwhile, rocuronium will start to take effect around 50-90 seconds. The net effect is that both drugs will take effect between ~45-90 seconds. This leads to a fairly short sedation lag time.
Keturonium (Ketamine then rocuronium)
If ketamine is given first, the kinetics are as shown above. The ketamine bolus will typically cause apnea and unconsciousness in ~30 seconds. However, the rocuronium is pushed later and it takes longer to work, so paralysis won't occur until 65-105 seconds. This creates a sedation lag time of about one minute during which the patient is apneic (from the ketamine), but not paralyzed.
This prolonged sedation lag time is dangerous for two reasons:
- First, as discussed above, this promotes desaturation and thereby reduces the amount of time that laryngoscopy can be performed safely.
- Second, there is a risk of initiating laryngoscopy after the ketamine has caused apnea, but before the rocuronium has taken effect. This is a natural mistake to make, because the patient is apneic and may seem to be paralyzed. However, the patient isn't truly paralyzed at this point in time, so they may still vomit and aspirate.
Midazolam pre-treatment before RSI?
On a related note, imagine a patient who is a bit anxious prior to intubation. Perhaps they should receive a dose of midazolam as an anxiolytic, to reduce the emotional stress of the peri-intubation period?
This is fine for most patients, but not a great idea for patients with severe respiratory failure. A little anxiety prior to intubation is physiologically beneficial to the patient, as this will cause:
- Tachypnea (may reduce pre-intubation PaCO2, preventing respiratory acidosis later on during the apneic period).
- Deep breathing (causes recruitment of lung bases, improving oxygenation).
I've gotten into trouble a few times by trying to be a nice guy and give midazolam before intubation to patients with respiratory failure. In some patients, this will cause somnolence which exacerbates hypoxemia and decruitment, thereby increasing the risk of peri-intubation desaturation. Thus, my current practice is generally to avoid any premedication if possible (one notable exception being that if the patient is truly unmanageable then delayed sequence intubation is indicated). This is part of the paradigm of taking a patient from full arousal to anesthesia very quickly:
Many standard textbooks recommend pushing the sedative prior to the paralytic. The principle guiding this sequence is that we would never want a patient to be paralyzed without sedation (anesthetic awareness). Hopefully this discussion has explained why pushing rocuronium immediately prior to ketamine won't cause anesthetic awareness.
Anesthetic awareness is a serious concern in the critical care arena. More realistic causes of awareness include:
- Not giving adequate sedation after intubation with rocuronium (the rocuronium out-lasts most sedatives provided during induction, so sedation must be re-dosed aggressively until paralysis wears off).
- Inadequate sedative doses in patients with a history of alcoholism and/or substance abuse (causing them to be refractory to standardized sedative dosing).
Additional strategies to prevent derecruitment during sedation/paralysis
Preoxygenation & apneic oxygenation
The cornerstones of achieving adequate safe laryngoscopy time are adequate preoxygenation and apneic oxygenation. Although critical, these have already been explored extensively here.
Patients who are awake may be encouraged to intentionally hyperventilate immediately preceding induction. The main effect of this is probably to drop the pre-induction PaCO2, thereby minimizing hypercapnia (3). It is possible that hyperventilation could improve recruitment and oxygenation as well.
Noninvasive ventilation during sedation/paralysis
Perhaps the most powerful strategy to reduce desaturation is noninvasive ventilation during sedation and paralysis. In short, this consists of attaching the patient to a BiPAP machine with a backup rate. As soon as the patient becomes apneic, the machine rate will immediately initiate gentle, controlled ventilation. Continuous administration of positive pressure avoids de-recruitment. Compared to manual ventilation, this has the advantage that it is seamless and provides perfectly-controlled breaths (unlike adrenergically-charged operators who tend to bag too hard).
Apneic ventilation using BiPAP generally works nicely, but it does depend on the ability to maintain a patent airway (e.g. gentle jaw thrust provided by the operator as the patient becomes sedated). There is no guarantee that it will work perfectly (2). Therefore, the best overall strategy may be to combine this with a rocuronium-ketamine sequence such that if the apneic ventilation fails, then the apneic time will still be limited.
Strategies to optimize laryngoscopy time may be summarized as follows:
- No benzodiazepine pre-treatment.
- Induction with high-dose rocuronium (e.g. 1.2-1.4 mg/kg) followed by ketamine.
- Adequate preoxygenation & apneic oxygenation.
- Voluntary hyperventilation before induction (if possible).
- In select high-risk patients, BiPAP with a backup rate may be used to provide positive pressure and gentle, controlled ventilation throughout this entire time period (VAPOX).
- Fresh commentary on this post by Scott Weingart here and Pharmacy Joe here. Huge thanks to Scott, Joe, and many other experts who have offered opinions here and on those sites. This is a true demonstration of FOAM, wherein open-sourced collaboration and debate has taken this beyond something that I could have created alone.
- VAPOX (a.k.a., vent-as-bag strategy during induction)(4)
- For example, Emergency Medicine Procedures by Reichman EF, 2nd edition, 2013, page 49.
- Note that even if the airway occludes, this strategy still works fairly well. Airway occlusion while on BiPAP will trap ~100% oxygen at positive pressure within the lungs. The positive pressure of the trapped oxygen will tend to keep the lungs open, preventing derecruitment. Unfortunately, airway occlusion will cause cessation of all ventilation, so PaCO2 will rise more rapidly than it would if the airway was open and there was ongoing ventilation. Thus, airway occlusion is potentially more problematic with regards to ventilation than oxygenation. In a situation where apneic ventilation was very important (e.g. severe metabolic acidosis), placing a nasal trumpet could be considered to improve ventilation during sedation and paralysis.
- Peri-intubation hypercapnia probably isn't a big issue for most patients (with some exceptions including patients with metabolic acidosis or elevated ICP). However, it is possible that peri-intubation hypercapnia causes peri-intubation hypertension in many patients (however, again, this generally isn't a big problem).
- Scott Weingart and I do VAPOX slightly differently. Either method will work fine. I would use whichever method you are more comfortable with (depends on which machines you use and how you generally set them up).
- IBCC chapter:Guide to APRV for COVID-19 - April 8, 2020
- PulmCrit Theoretical Post – The COVID Severity Index (CSI 1.0) - April 2, 2020
- PulmCrit wee – Why the SCCM/AARC/ASA/APSF/AACN/CHEST joint statement on split ventilators is wrong. - March 29, 2020