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Radial to Femoral Arterial Blood Pressure Differences in Septic Shock Patients Receiving High-Dose Norepinephrine Therapy

Kim, Won Young*; Jun, Jong Hun; Huh, Jin Won; Hong, Sang Bum; Lim, Chae-Man; Koh, Younsuck

doi: 10.1097/SHK.0000000000000064
Clinical Aspects
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ABSTRACT Objectives: The accuracy of arterial blood pressure (ABP) monitoring is crucial in treating septic shock patients. Clinically significant differences in central to peripheral ABP could develop into sepsis during vasopressor therapy. The aim of this study was to investigate the difference between radial (peripheral) and femoral (central) ABP in septic shock patients receiving high-dose norepinephrine (NE) therapy. Methods and Results: This prospective observational study comparing simultaneous intra-arterial measurements of radial and femoral ABP was performed at a university-affiliated, tertiary referral center between October 2008 and March 2009. Patients with septic shock who needed continuous blood pressure monitoring and high-dose NE therapy 0.1 µg/kg per minute or greater to maintain mean arterial pressure (MAP) of 65 mmHg or greater were included. Statistical analysis was conducted using the Bland-Altman method for comparison of repeated measures. In total, 250 sets of systolic, mean, and diastolic femoral and radial ABP were recorded at baseline and after NE titration. Arterial blood pressure readings from the radial artery were underestimated compared with those from the femoral artery. Overall bias (mean difference between simultaneous measurements) between radial and femoral MAP was +4.9 mmHg; however, during high-dose NE therapy, the bias increased to +6.2 mmHg (95% limits of agreement: −6.0 to +18.3 mmHg). Clinically significant radial-femoral MAP differences (MAP ≥5 mmHg) occurred in up to 62.2% of patients with high-dose NE therapy. Conclusions: Radial artery pressure frequently underestimates central pressure in septic shock patients receiving high-dose NE therapy. Femoral arterial pressure monitoring may be more appropriate when high-dose NE therapy is administered.

*Department of Emergency Medicine, Asan Medical Center; Department of Anesthesiology and Critical Care Medicine, Hanyang University College of Medicine; and Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea

Received 22 Jul 2013; first review completed 11 Aug 2013; accepted in final form 24 Sep 2013

Address reprint requests to Younsuck Koh, MD, PhD, Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, 388-1, Pungnap-2 dong, Songpa-gu, Seoul, South Korea. E-mail: yskoh@amc.seoul.kr.

No funding or supporting agencies were involved in this study.

The authors state that they have no conflicts of interest regarding the publication of this article.

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INTRODUCTION

Invasive arterial blood pressure (ABP) monitoring is fundamental during shock management in the intensive care unit (ICU) (1). The Surviving Sepsis Campaign international consensus guidelines recommend maintaining a mean arterial pressure (MAP) of 65 mmHg or greater, as a goal of initial resuscitation, and to apply vasopressors to maintain MAP at this level (2). Inaccurate monitoring of MAP could lead to improper treatment in the form of excessive fluid infusion or unnecessary vasopressor therapy; therefore, accurate ABP monitoring is crucial in treatment of septic shock.

Although debate persists on the ideal monitoring site, in practice, the radial artery is the most common cannulation site because of well-documented low complication rates and easy access. However, some studies have repeatedly demonstrated inconsistencies between femoral (central) and radial (peripheral) ABP after cardiopulmonary bypass (3–6) and in clinical situations, including hypothermia (7, 8) and liver transplantation (9–12). The adequacy of the radial artery as a site for ABP monitoring in septic shock patients receiving high-dose vasopressors has not been carefully examined. A previous study showed that radial ABP monitoring significantly underestimates femoral ABP during vasopressor therapy in critically ill patients and suggested that inserting a femoral line substantially reduced the infusion rate of vasoactive drugs (11). However, a recent study (13) reported that radial and femoral MAPs showed good agreement regardless of the use of vasoactive drugs. Unfortunately, in these studies, both the patient population and the vasoactive drug used were not homogeneous, and the results could not be extrapolated to critically ill patients found in a medical and surgical ICU. The equivalence of central and peripheral ABP monitoring in critically ill patients with septic shock remains controversial. If measuring ABP peripherally leads to an underestimation of central blood pressure, then excessive vasopressor or fluid therapy may be used.

The present observational clinical study was conducted to test the hypothesis that radial and femoral ABP measurements are significantly different in septic shock patients receiving high-dose norepinephrine (NE) therapy.

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METHODS

Study design and population

This was a prospective observational study comparing simultaneous intra-arterial measurements of radial and femoral ABP carried out in a medical ICU at a university-affiliated, tertiary referral center between October 2008 and March 2009. Following approval from the local research ethics committee and written, informed patient consent, we studied patients with septic shock who needed continuous blood pressure monitoring during high-dose NE therapy (≥0.1 µg/kg per minute) to maintain MAP of 65 mmHg or greater. Patients were excluded if they were experiencing immunodepression (absolute neutrophil count <500/mm3), coagulopathy (prothrombin time <1.5 or platelet count <50,000/[mu]L), severe anemia (hemoglobin <6.0 g/dL), prone position, an abnormal Allen test, induced hypothermia, significant aortic valvular disease, or known vascular disease (Fig. 1). All patients were managed according to the Surviving Sepsis Campaign guidelines, including initial resuscitation bundles, infection control, hemodynamic support, and adjunctive therapy (2).

Fig. 1

Fig. 1

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ABP measurements

After a patient’s enrolment, both same-side radial and femoral arteries were cannulated, and intra-ABP was simultaneously monitored. For radial arteries, a 20-gauge, 4.5-cm Teflon catheter (BD Angiocath Plus; Becton Dickinson, Seoul, Korea) was used; for femoral arteries, a 20-gauge, 20-cm catheter (BD First Midcath; Becton Dickinson) was used. Both catheters were connected to 100-cm saline-filled, rigid manometer lines with a single 3-way stopcock to a pressure transducer (DTX PLUS DT 4812, BD Infusion Therapy Systems; Becton Dickinson). These were leveled to the right atrium and zeroed to atmospheric pressure. Arterial pressure waveforms and systolic, mean, and diastolic femoral and radial ABPs were simultaneously recorded on the bedside monitor (M1205A 24CT; Hewlett Packard, Andover, Mass). Arterial pressure waveforms were frequently evaluated using a rapid flush test to rule out occlusion or catheter malposition. After being in a steady, supine position, the systolic, mean, and diastolic femoral and radial ABPs were simultaneously measured at baseline (10 min after the insertion of the second catheter) and after subsequent NE dose titrations (10 min after changing the NE dose). Blood pressure were recorded at the following points according to our protocol for titrating the NE dose: (1) baseline: after both arterial cannulations, (2) low dose (NE <0.1 µg/kg per minute): tapering 50% (0.08, 0.04, 0.02 µg/kg per minute, and stop), (3) high dose (0.1 µg/kg per minute ≥ NE < 0.3 µg/kg per minute): tapering 20% (0.24, 0.2, 0.16, 0.12, and 0.1 µg/kg per minute), (4) very high dose (NE ≥0.3 µg/kg per minute): with a 0.1 decrease (Fig. 1). Measurements were taken three times every 5 min. After 3 days, the femoral artery catheter was removed.

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Statistical analysis

Continuous variables are expressed as mean ± SD or medians and interquartile ranges if the assumption of a normal distribution was violated. Categorical variables are expressed as numbers and percentages. Clinically significant MAP differences were defined as MAP differences of 5 mmHg or greater (8, 14). Bland-Altman analyses (15) were performed to test whether the femoral and radial blood pressure were statistically different. Bias, precision, and 95% limits of agreement of the simultaneous measurements were calculated and compared in patients receiving high-dose and low-dose NE. Wilcoxon signed rank test was used to compare differences in bias and precision. Spearman rank correlation was used to determine the relationship between the NE dose and ABP. All statistical analyses were performed using SPSS for Windows, version 20.0 (SPSS Inc, Chicago, Ill), and a two-tailed P < 0.05 was considered statistically significant.

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RESULTS

During the study period, a total of 159 patients with septic shock were admitted to the ICU. Of these, 109 patients were receiving high-dose NE therapy to maintain MAP of 65 mmHg or greater. We excluded 72 patients (18 patients with immunodepression, 39 patients with coagulopathy, 10 patients who refused to be part of the study, and five patients due to other causes), leaving a total of 37 patients for analysis (Fig. 1). The demographic and clinical characteristics of these patients are shown in Table 1. The mean age was 66.7 years, and 71.4% were male. The primary origin of sepsis was pulmonary (53.6%), hepatobiliary (15.2%), intra-abdominal (8.8%), urinary (7.6%), and others/unknown (14.8%).

Table 1

Table 1

In total, 250 sets of systolic, mean, and diastolic femoral and radial ABP recordings were obtained. All patients recorded systolic, mean, and diastolic femoral and radial ABPs at high-dose NE levels; 30 patients recorded systolic, mean, and diastolic femoral and radial ABPs at low-dose NE levels, and 27 patients recorded systolic, mean, and diastolic femoral and radial ABPs when NE administration was stopped because NE tapering did not occur within 3 days in six patients, and four patients died before NE tapering (Table 1). Systolic, mean, and diastolic femoral and radial ABP data based on NE doses are presented in Table 2. The mean value of the ABP data from the radial artery was lower than that from the femoral artery. Arterial blood pressure values from the radial artery were significantly different between high- and low-dose NE therapy. These differences were not observed when readings were taken from the femoral artery (Table 2).

Table 2

Table 2

Table 3 shows that femoral MAP was higher than radial MAP. This was more frequently seen in high-dose NE therapy than in low-dose NE therapy. Twenty-three patients (62.2%) had clinically significant femoral-radial MAP differences, and 10 patients (27.0%) had a discrepancy that was greater than 10 mmHg. Furthermore, clinically significant MAP differences occurred more frequently in high-dose than in low-dose NE infusion (57.7% vs. 30.7%, P < 0.01). In our study, we also found that femoral-radial MAP differences had a significantly positive correlation with the dose of NE therapy received (r = 0.33, P < 0.01).

Table 3

Table 3

Table 4 shows mean values of ABP variables obtained using both arterial catheters and bias (mean difference between simultaneous measurements) between ABP measurements with corresponding 95% limits of agreement. Bland-Altman graphs for high- and low-dose NE are shown in Figure 2. With high-dose NE levels, there were marked discrepancies in femoral and radial MAP, with a bias of +6.2 mmHg (95% limits of agreement: −6.0 to +18.3 mmHg). There were also marked discrepancies in systolic and diastolic arterial pressure, with a bias of +5.3 mmHg (95% limits of agreement: −14.8 to +25.5 mmHg) and a bias of +6.2 mmHg (95% limits of agreement: −7.5 to +19.9 mmHg) (Fig. 2A). However, at low-dose NE levels, the bias was modest. The bias for MAP was +3.0 mmHg (95% limits of agreement: −7.2 to +13.1 mmHg); for systolic ABP, it was +2.4 mmHg (95% limits of agreement: −14.5 to +19.3 mmHg), and for diastolic ABP, it was +3.0 mmHg (95% limits of agreement: −9.7 to +15.8 mmHg) (Fig. 2B). Femoral to radial mean, systolic, and diastolic ABP differences were significantly higher for high-dose NE therapy than for low-dose NE therapy (all P < 0.01).

Table 4

Table 4

Fig. 2

Fig. 2

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DISCUSSION

We investigated the differences between radial and femoral ABP in patients with septic shock receiving high-dose NE therapy. The main findings of our study were as follows: (i) radial artery ABP readings were underestimated compared with those taken from the central artery, and this was more marked in patients receiving high-dose NE therapy; (ii) overall, the mean bias between radial and femoral MAP was +4.9 mmHg, but during high-dose NE therapy, the mean bias increased to +6.2 mmHg (95% limits of agreement: −6.0 to +18.3 mmHg); (iii) clinically significant radial-femoral MAP differences were frequently observed (62.2%) in high-dose NE therapy.

Arterial pressure monitoring is of fundamental importance in patients with septic shock, yet few studies have examined the differences between central and peripheral ABP values in this population. Our results showed large discrepancies in MAP measured at the radial and femoral site in septic shock patients receiving high-dose NE therapy. These results are consistent with an earlier study by Dorman et al. (11), where a proportion of patients receiving vasoactive agents showed marked differences in radial and femoral MAP values. However, Mignini et al. (13) suggested radial and femoral pressures were interchangeable, with a small overall MAP difference of +3 (95% limits of agreement of 16 mmHg). Discrepancies between our results and those reported by Mignini and colleagues might be related to the study population (critically ill patients in a surgical ICU) and differences in the vasoactive drug administered (only 30.9 patients received NE therapy).

Central-peripheral MAP differences are not uncommon and have been repeatedly demonstrated in surgical patients undergoing cardiopulmonary bypass and liver transplantation. However, the responsible mechanisms are poorly understood (5, 6, 10, 12). A similar phenomenon may occur in patients with septic shock, especially in those receiving high-dose NE therapy. In the present study, we compared MAP values in patients receiving high- and low-dose NE therapy, and we observed significant differences between these two groups when readings were taken from the radial artery. By contrast, when readings were taken from the femoral artery, such differences were not observed (Table 2). This means that MAP monitoring from the peripheral artery is more susceptible to NE therapy than that from the central artery. Vasopressor therapy for septic shock is common in most ICUs. Erroneously, a low radial ABP may result in unnecessary fluid challenge or the dose up of already applied vasoconstrictors to raise the ABP, which could induce pulmonary edema, tachyarrhythmia, and vasoconstrictor-induced renal, hepatic, or splanchnic ischemia.

This study confirms the high prevalence of clinically significant MAP differences in septic shock patients receiving high-dose NE therapy, with up to 62% of patients with a MAP difference of 5 mmHg or greater and 27% of patients with a MAP difference of 10 mmHg or greater. These results suggest that, in patients with marginally maintained MAP measured at the radial artery under high dose of NE therapy, the MAP measurement at femoral artery may be necessary to avoid potentially harmful fluid challenge or dose increase of vasopressors. In these patients, the femoral artery may be the preferred site for arterial pressure monitoring. Although some authors caution against the use of the femoral artery for fear of higher complication rates (16), the actual incidence for major complications, such as ischemic damage, infection, and pseudoaneurysm formation, is equally low (<1%) for both radial and femoral arteries (17). Furthermore, the femoral artery is usually palpable even in hypotensive patients and may be the only accessible route for hemodynamic monitoring.

This study was limited by the small sample size and the fact that it was performed only on septic shock patients, which does not necessarily allow extrapolation to other critically ill patient populations. Another potential concern is that we could not evaluate exact volume status except central venous pressure. This may have led to an underestimation or overestimation of pressure difference.

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CONCLUSIONS

Radial artery pressure frequently underestimates central pressure in septic shock patients receiving high-dose NE therapy. Femoral arterial pressure monitoring may be more desirable when high-dose NE therapy is administered.

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Keywords:

Femoral artery; radial artery; arterial pressure monitoring; measurement techniques; vasoconstrictor agents; sepsis

© 2013 by the Shock Society