I’m afraid she will tank after intubation, could you start some fluid?
I brought a liter of fluid, just in case the blood pressure falls after intubation.
He is decompensating! Run the fluid wide open!
We’ve all probably heard and spoken those phrases. Crystalloid is a traditional therapy in efforts to either prevent or mitigate hypotension induced by intubation. But is there good evidence to support this common practice?
PREPARE trial: overview
This is a pragmatic, multi-center RCT investigating patients undergoing intubation.1 Eight sites were ICUs and one was an emergency department – so this was predominantly an ICU study. Prior to intubation, patients were randomized to receive a 500-ml fluid bolus versus no bolus. The primary endpoint was a composite of post-intubation complications including new-onset hypotension (systolic Bp <65 mm), new or increased vasopressor administration, or cardiac arrest.
The study was stopped early for futility after enrolling 337 patients. Although premature study termination is often a mistake, it seems like a rational decision here. The outcomes in both groups are exactly the same (figure above). There isn’t even a hint of any possible signal.
should we be surprised by this result?
I was surprised by this result. However, upon further consideration, I shouldn’t have been. This is generally how studies on fluid boluses go – we are expecting benefit, but are disappointed by the results. Because when you drill down on the evidence surrounding fluid bolus therapy, it’s often shockingly poor.
Glassford et al. performed an exhaustive systematic review of fluid bolus therapy in sepsis.2 They found 33 studies using a variety of bolus sizes (500 ml was the most commonly used volume). Among these, 10 studies reported the immediate hemodynamic effect of a fluid bolus. The median effect on blood pressure was a mere seven-millimeter increase:
A seven-millimeter increase in blood pressure has minimal clinical significance. If you cycle the blood pressure cuff twice in a row during an intubation, the blood pressure will likely fluctuate by >7 mm simply due to ongoing physiologic variations. A difference of this magnitude is unlikely to affect the endpoints of the PREPARE trial (or have clinically meaningful effects).
One additional factor further explains lack of efficacy of fluid bolus therapy the PREPARE trial. The fluid bolus was initiated prior to intubation, but in most cases only about half of the bolus could be administered prior to laryngoscopy. I wouldn’t view this as a limitation of the trial, but rather a strength of the trial – as a pragmatic study, it is accurately reporting on the reality of fluid boluses. And that reality is that they take a while to infuse. It’s dramatic to yell “run the fluid wide open,” but the reality is that it still only drips in.
physiology behind why fluid boluses don’t work
Overall, the evidence supports following points:
- Fluid boluses generally don’t have a substantial effect on blood pressure (e.g. >20 mm).
- Any effect of a fluid bolus on blood pressure is usually short-lived.
- Fluid boluses overall are a relatively inefficient approach to treating hypotension.
What is the physiology behind this? There are many reasons why patients may not respond to fluid boluses, most notably:
- Only about half of critically ill patients are fluid-responsive at all (many patients are operating on the flat portion of the Starling curve and will see no benefit from additional preload).
- Even if the patient is fluid-responsive, fluid administration may cause a reflexive decrease in endogenous sympathetic tone. This will result in an increase in cardiac output with a neutral effect on blood pressure.
- Administered fluid often rapidly extravasates out of the vascular space, so any transient benefit is rapidly lost.
The following video explores this a bit further:
In fairness, there is definitely a subset of patients who have severe pre-existing hypovolemia (e.g. borderline hypovolemic shock). Such patients are at increased risk of post-intubation hemodynamic deterioration. In that subset of patients, volume administration before intubation does make sense. However, such patients are uncommon – especially among ICU patients, who have likely already received some fluid resuscitation in the emergency department. It’s possible that fluid bolus therapy would be more effective among emergency department patients, who might have a greater rate of uncorrected hypovolemia.
superiority of vasopressors over fluid for peri-intubation hypotension
There are numerous reasons that vasopressors are superior to fluid boluses in the peri-intubation period:
- Vasopressors are simply more effective at increasing the blood pressure. For example, this has been shown in septic shock – early vasopressor leads to faster shock resolution compared to a fluid-first strategy. Fluids will only cause only a mild improvement in blood pressure, failing to stabilize lots of patients. In contrast, vasopressors will stabilize nearly all patients.
- Vasopressors are faster. A vasopressor infusion can bring up the blood pressure in several minutes, or a push-dose vasopressor can bring up the blood pressure in seconds. Conversely, there are hard limits to how rapidly a fluid bolus can be infused.
- Vasopressors are more titratable. We’re often worried about hypotension when we intubate patients, so initially our goal is often to increase the blood pressure. However, sometimes the stimulation of intubation or medications (e.g. ketamine) may actually push the blood pressure too high. If we used a vasopressor to increase the pressure, that’s fine – just down-titrate the vasopressor. Alternatively, if we gave the patient an excessive volume of fluid, there’s no rapid way to reverse that.
- Vasopressors avoid fluid overload. We are often intubating patients due to hypoxemic respiratory failure – a disorder which doesn’t respond well to large volumes of fluid.
Historically, we used a fluid-first strategy due to fears surrounding the use of peripheral vasopressors. However, now that these fears have been allayed, it makes sense to switch to a strategy of using IV vasopressor to stabilize patients in the peri-intubation period.
The real question here isn’t fluids vs. vasopressor, but rather exactly when and how is the best way to provide vasopressor. My personal preference is to initiate a vasopressor infusion early if there is concern for hypotension, to establish a systolic Bp over about 120 mm before intubation (to provide a cushion in case blood pressure drops). In other cases, I might simply have a vasopressor infusion in the room and ready to start. Exactly which patients might benefit from which strategy? Some evidence surrounding this practice might help guide management.
- Fluid boluses are ineffective for supporting blood pressure in the peri-intubation period during intubation of ICU patients. There are numerous reasons for this, including lack of fluid responsiveness and the long duration required to give a fluid bolus.
- Lack of a clinically significant effect of fluid boluses on blood pressure has been demonstrated previously in a systematic review of prospective trials in septic shock. This is now confirmed in the PREPARE trial, a prospective multi-center pragmatic study.
- There are numerous reasons that vasopressors are potentially superior to fluid for hemodynamic stabilization of the peri-intubation patient: greater efficacy, faster onset, greater titratability, and avoidance of fluid overload.
- If a patient is believed to be volume depleted and this hypovolemia is felt to be detrimental, then fluid resuscitation is indicated. The decision to provide fluid should ideally be driven by the patient’s hypovolemic status, rather than a fleeting desire to improve hemodynamics during intubation.
- If you’re bringing a liter bag of fluid into a high-risk intubation with hopes of staving off hemodynamic decompensation, you’re bringing a knife to a gunfight.
- PREPARE trial with Dave Janz (5MinuteAirway, Terren Trott) – Contains interview with lead author.
- Myth-busting the fluid bolus (PulmCrit)
- 1.Janz D, Casey J, Semler M, et al. Effect of a fluid bolus on cardiovascular collapse among critically ill adults undergoing tracheal intubation (PrePARE): a randomised controlled trial. Lancet Respir Med. October 2019. https://www.ncbi.nlm.nih.gov/pubmed/31585796.
- 2.Glassford N, Eastwood G, Bellomo R. Physiological changes after fluid bolus therapy in sepsis: a systematic review of contemporary data. Crit Care. 2014;18(6):696. https://www.ncbi.nlm.nih.gov/pubmed/25673138.