a b s t r a c t

Study objectives: Hypotension is a common side effect of propofol, but there are no reliable methods to determine which patients are at risk for significant propofol-induced hypotension (PIH). Ultrasound has been used to esti- mate volume status by visualization of Inferior vena cava collapse. This study explores whether IVC assess- ment by ultrasound can assist in predicting which patients may experience significant hypotension.

Methods: This was a prospective observational study conducted in the operating suite of an urban community hospital. A convenience sample of consenting adults planned to receive propofol for induction of anesthesia dur- ing scheduled surgical procedures were enrolled. Bedside ultrasound was used to measure maximum (IVCmax) and minimum (IVCmin) IVC diameters. IVC-CI was calculated as [(IVCmax-IVCmin)/IVCmax x 100%]. The prima- ry outcome was significant hypotension defined as systolic Blood pressure below 90 mmHg and/or admin- istration of a vasopressor to increase BP during surgery.

Results: The study sample comprised 40 patients who met inclusion criteria. Mean age was 55 years, (95%CI, 49-60) with 53% female. 55% of patients had significant hypotension after propofol administration. 76% of pa- tients with IVC-CI >= 50% had significant hypotension compared to 39% with IVC-CIb 50%, P = .02. IVC-CI >= 50% had a specificity of 77.27% (95%CI, 64.29%-90.26%) and sensitivity of 66.67% (95%CI, 52.06%-81.28%) in predicting PIH. The odds ratio for PIH in patients with IVC-CI >= 50% was 6.9 (95%CI, 1.7-27.5).

Conclusion: Patients with IVC-CI >= 50% were more likely to develop significant hypotension from propofol. IVC ul- trasound may be a useful tool to predict which patients are at increased risk for PIH.

(C) 2016

Introduction

Propofol is a short acting intravenous Anesthetic agent, routinely used as an Induction agent in general anesthesia. Due to its rapid onset, effec- tiveness and short Recovery time, it has gained popularity with Emergency Physicians in providing deep sedation. Hypotension has been shown to be a common side-effect of propofol administration, with rates as high as 49% [1]. It is unclear if this induced drop in blood pressure causes any clinically significant effects on patient outcomes. However, longer postoperative stays and higher Death rates are associated with postinduction hypoten- sion [2]. Additionally, hypotensive events in the emergency department (ED) have been correlated to higher death rates during hospitalization [3].

Predicting propofol induced hypotension (PIH) may have the potential to prevent iatrogenesis. Rates of PIH are highest in patients greater than

? Funding Sources/Disclosures: None.

?? Prior Presentations: Presented as preliminary results at the American College of Emer- gency Physicians Annual Conference, October 2014, Chicago, IL.

* Corresponding author at: 1020 Sansom Street, Suite 239 Thompson Buildling, Philadelphia, PA, 19107. Tel.: +1 215 955 6844; fax: +1 215 923 6225.

E-mail address: arthur.au@jefferson.edu (A.K. Au).

50 years of age, with pre-existing hypotension and American Society of Anaesthesiologists’ Physical Status (ASA-PS) of class II or greater [2]. Addi- tionally, patients with lower intravascular volume status may be more likely to have PIH, but this has not been explored. The current study set out to determine if lower intravascular volume status, as measured by ul- trasound, can predict significant hypotension. We hypothesized that an IVC-CI >= 50% would be associated with a higher rate of significant hypoten- sive events in patients receiving a bolus dose of intravenous propofol.

Materials and methods

Design

This was a prospective observational study conducted in the surgical suite of an urban community hospital.

Population

A convenience sample of consenting adult patients planned to re- ceive propofol for induction of anesthesia during scheduled, non-

http://dx.doi.org/10.1016/j.ajem.2016.03.058

0735-6757/(C) 2016

1126 A.K. Au et al. / American Journal of Emergency Medicine 34 (2016) 1125–1128

emergent, surgical procedures were enrolled over a 4-week period from March – April 2014. Patients planned to receive propofol were screened by an anesthesiologist and included if they were scheduled for uncom- plicated procedures with minimal blood loss expected. Patients were excluded if they had a history of heart failure or valvular heart disease, were under the age of 18 or unwilling to consent. All enrolled patients underwent informed consent and the study was approved by the institution’s internal review board.

Protocol

Patients were screened and enrolled in the preoperative suite on the day of their scheduled procedures. Enrolled patients were placed in su- pine position and baseline Blood pressure and heart rate was recorded. ultrasound images of the IVC were then obtained using either the subxiphoid or intercostal window. The IVC was visualized and 6- second clips were recorded in both longitudinal and transverse planes. IVC measurements were made using M-mode in the transverse plane, as measuring in the longitudinal plane can lead to off-midline measure- ments which result in smaller IVC diameter measurements [4]. Maxi- mum (IVCmax) and minimum (IVCmin) IVC diameters were measured approximately 2 cm below the entry of the hepatic veins dur- ing a normal respiratory cycle. IVC-CI was calculated as [(IVCmax- IVCmin)/IVCmax x 100%] [5]. Ultrasounds were performed by physi- cians with Fellowship training in emergency ultrasound and had each previously performed greater than 20 IVC ultrasounds. All deidentified clips and measurements were reviewed by another Blinded physician to ensure that measurements were of adequate quality.

Research assistants, blinded to IVC measurements, traveled with the patients to the operating suites, where they recorded vital signs every 3 minutes from the beginning of surgery until 21 minutes after propofol administration. All intraoperative medication and fluid administration was also recorded. Treating anesthesiologists were also blinded to the

preoperative IVC measurements. All medications, including propofol and vasopressors, were dosed at the discretion of the anesthesiologists. The primary outcome was significant hypotension defined as a sys- tolic blood pressure (BP) below 90 mmHg and/or administration of a va- sopressor to increase BP within 21 minutes after the administration of propofol. Assuming an approximate 50% rate of PIH, we hypothesized that patients with an IVC-CIb 50% would have a low rate (b 10%) of PIH whereas patients with an IVC-CI >= 50% would have a high (>= 75%) rate of PIH. To detect this difference, it was determined that 13 patients needed to be enrolled in each IVC group. Because patients were enrolled randomly, without prior knowledge of IVC-CI, at least 10 additional pa- tients would be required to ensure enough patients in each group to de-

tect the outcome of interest.

Data Analysis

Summary statistics were generated for the participants’ characteris- tics (age, sex, BMI), preoperative vital signs (pulse rate, systolic blood pressure, diastolic blood pressure), and primary study measurements (IVCmin, IVCmax and IVC-CI). Participants were stratified by Incidence of PIH. Their characteristics, vital signs and primary study measure- ments were compared by calculating the difference in mean values or proportions between those with and without PIH. Corresponding 95% confidence intervals (CIs) of the differences were calculated. Differences were considered significant at the P = .05 levels for all analyses. Perfor- mance characteristics of the ability of an IVC-CI >= 50% to predict PIH were calculated, along with corresponding 95% CIs.

Results

A total of 51 patients were enrolled in the study. IVC ultrasounds were performed by 5 different physicians. One patient was excluded due to a history of aortic stenosis. 10 additional patients were excluded due to inadequate imaging quality. This resulted in 40 patients meeting

Table 1

Comparison of participants by incidence of propofol induced hypotension.

Participant Characteristics	All participants,	Propofol induced hypotension	No propofol induced hypotension
	n = 40	n = 18	n = 22
Demographics, mean (95%CI)
Age, y	55 (95%CI,49-60)	58 (95%CI,49-66)	53 (95%CI,45-61)
Female, %	53% (95%CI,36-68)	57% (95%CI,34-78)	43% (95%CI,22-66)
Male, %	47% (95%CI,32-64)	32% (95%CI,13-57)	68% (95%CI,43-87)
BMI, (kg/m2)	29 (95%CI,27-30)	28 (95%CI,25-30)	29 (95%CI,27-32)
Preoperative Vital signs, mean (95%CI)
Pulse rate, (beat/min)	73 (95%CI,68-77)	75 (95%CI,68-82)	70 (95%CI,65-75)
Systolic BP, mmHg	141 (95%CI,135-147)	135 (95%CI,126-144)	146 (95%CI,138-153)
Diastolic BP, mmHg	77 (95%CI,74-80)	75 (95%CI,70-79)	79 (95%CI,75-83)
Propofol dose and inferior vena cava Measurements, mean (95%CI)
Propofol dose (mg/kg)	2.4 (95%CI,2.2-2.6)	2.4 (95%CI,2.2-2.7)	2.3 (95%CI,2.1-2.6)
IVCmax, cm	1.6 (95%CI,1.5-1.8)	1.6 (95%CI,1.5-1.8)	1.7 (95%CI,1.5-1.9)
IVCmin, cm	1.0 (95%CI,0.8-1.1)	0.9 (95%CI,0.7-1.1)	1.0 (95%CI,0.9-1.2)
IVC-CI	41 (95%CI,35-47)	44 (95%CI,35-54)	38 (95%CI,31-46)
Operative Variables
Procedure Type
Gynecologic	7	5	2
Otolaryngologic	2	2	0
Orthopedic	18	6	12
Urologic	6	3	3
General Surgical	7	5	2
Paralytics
Administered	13	6	7
Not Administered	27	12	15
Airway Type
Endotracheal Intubation	25	12	13
Laryngeal Mask	11	3	8
General Mask	3	2	1
Tracheostomy	1	1	0

A.K. Au et al. / American Journal of Emergency Medicine 34 (2016) 1125–1128 1127

Table 2

2×2 Table of IVC-CI >= 50% and Propofol Induced Hypotension.

+ Hypotension – Hypotension

IVC-CI >= 50% 12 5

IVC-CIb 50% 6 17

Test Characteristics of an IVC-CI of >=50% for predicting PIH. Sensitivity 66.67% (95%CI,52.06-81.28).

Specificity 77.27% (95%CI,64.29-90.26).

Positive predictive value 70.59% (95%CI,56.47-84.71). Negative predictive value 73.91% (95%CI,60.31-87.52). Odds Ratio 6.9 (95%CI,1.7-27.5).

all inclusion criteria. Demographics of the study population and a com- parison of the participants by the presence or absence of PIH are provid- ed in Table 1. Mean age was 55 years, (95%CI, 49-60) with 53% female. There were no differences in age, sex, BMI or preoperative vital signs be- tween the two groups. Operative procedures included 7 gynecologic, 18 orthopedic, 6 urologic, 2 ENT and 7 general surgeries. None of these pro- cedures resulted in significant blood loss. 13 patients received paralytic medications in addition to Propofol during their procedures (Table 1).

On average, patients received 2.4 mg/kg (95%CI, 2.2-2.6) boluses of propofol during induction. 55% of all patients had significant hypoten- sion after propofol administration. 19 of these patients were given vaso- pressors during their procedures. 76% of patients with a IVC-CI >= 50% had significant hypotension compared to 39% with a IVC-CIb 50%, P = .02. The performance characteristics of the presence of an IVC- CI >= 50% in predicting PIH are shown in Table 2. IVC-CI >= 50% has a spec- ificity of 77.27% (95%CI, 64.29%-90.26%) and sensitivity of 66.67% (95%CI, 52.06%-81.28%) in predicting PIH. The odds ratio for PIH in pa- tients with an IVC-CI >= 50% was 6.9 (95%CI, 1.7-27.5). In patients who developed significant hypotension, hypotension occurred on average 9 minutes (SD 7.5) after propofol was administered.

Discussion

This study investigated the association of preprocedural IVC-CI as measured by bedside ultrasonography with incidence of intraoperative PIH. We found that a preoperative IVC-CI >= 50% was associated with a greater rate of PIH. Having a Predictive tool to ascertain whether a spe- cific individual is likely to become hypotensive could prove useful when a provider is choosing sedation agents, respective dosages and potential preprocedural hydration.

Propofol is a commonly employed anesthetic agent used by Emer- gency Physicians during procedures requiring deep sedation. A com- monly encountered complication of propofol administration is PIH, with an incidence as high as 49% in certain study populations [1]. Addi- tionally, it has been demonstrated that hypotensive events in the ED are associated with increased mortality during hospitalization [3]. Hypoten- sion during sedation also creates an additional burden on the physician, as attention must be placed on reducing the degree of hypotension. This often includes administration of intravenous fluid, reduction of subse- quent propofol doses, addition of vasopressors with their inherent side effects and selection of an alternative agent for the remainder of the sedation [6]. These can all lead to attention being taken away from the other elements of the sedation as well as the planned procedure.

Multiple prior studies have attempted to identify risk factors for PIH. The current literature suggests that PIH is highest in patients greater than 50 years of age, with pre-existing hypotension and American Soci- ety of Anaesthesiologists’ Physical Status (ASA-PS) of class II or greater [2]. PIH is thought to be due to decreased systemic vascular resistance or cardiac output from arterial and venous vasodilation [7]. With this mechanism in mind, prior authors have attempted to prevent PIH by volume loading or premedicating with ephedrine, with varying amounts of success [8,9]. While there may be a potential benefit to premedicating with ephedrine or Fluid loading, this has not been uni- versally recommended. Ephedrine causes a significant increase in

heart rate and post-induction hypertension while failing to protect against delayed hypotension [8]. Preprocedural volume loading has been shown to decrease rates of PIH, however these studies have gener- ally been isolated to patients less than 50 years of age and with ASA-PS of class I or II. These studies do not advocate the use of prophylactic vol- ume loading in patients greater than 50 years of age [9].

Ultrasound of the IVC has been shown to correlate with central ve- nous pressure and assist with determining a patient’s overall volume status [10]. In the present study, ultrasound evaluation of the IVC was considered as a potential means to determine which individual patients were more likely to become hypotensive after an IV bolus of propofol. Our results indicate that patients with an IVC-CI >= 50% prior to propofol administration are more likely to become hypotensive.

Ultrasound evaluation of the IVC can be rapidly performed and is considered technically straightforward, requiring minimal training in which to become competent. Employing this prior to sedation with propofol may help indicate which patients are likely to become hypo- tensive and could be a useful adjunct in assisting the provider with de- cisions on sedation agents, propofol dosage levels, and usage of prophylactic intravenous fluids. This may be particularly useful in pa- tients over the age of 50 with an unclear preprocedural volume status. By obtaining an IVC-CI, a provider may quickly see that a patient is both volume depleted, as well as more likely to develop PIH. In this scenario, the provider could preload a patient with fluids without the concern for overloading or causing acute pulmonary edema. Future studies must be done to evaluate the effectiveness of volume loading patients with IVC-CI >= 50%, to see if this significantly reduces PIH in these patients.

Limitations

There are several limitations of the current study. The sedations took place in the operating room suites and did not specifically involve ED patients. ED patients receiving sedation are not always as healthy and prepped as the outpatient surgical population. The dosages of propofol that patients received were also variable and may reflect a different practice pattern between Anesthesiologists and Emergency Physicians. Ultrasound was performed by fellowship trained sonographers, so the results may not be generalizable to less experienced operators. All IVC measurements were reviewed by a blinded expert, but scan acquisition was still open to variability dependent on the operator. 20% of patients were excluded due to inability to adequately visualize and measure the IVC which may have affected results.

Conclusions

The results of this study suggest that patients with an IVC-CI >= 50%, as assessed by ultrasound, are more likely to develop significant hypo- tension after receiving propofol for sedation. More research is needed to determine the reproducibility of these results, as well as their appli- cability to the ED patient population.

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