Pulse-Oximetric Measurement of Prilocaine-Induced Methemoglobinemia in Regional Anesthesia : Anesthesia & Analgesia

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Analgesia: Brief Report

Pulse-Oximetric Measurement of Prilocaine-Induced Methemoglobinemia in Regional Anesthesia

Soeding, Peter MD*; Deppe, Matthias*; Gehring, Hartmut MD, PhD*

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Anesthesia & Analgesia 111(4):p 1065-1068, October 2010. | DOI: 10.1213/ANE.0b013e3181eb6239

Prilocaine, in comparison with all other local anesthetics, has the lowest direct systemic toxicity, but may lead to an increased formation of methemoglobin (MetHb).1,2 Whereas in healthy individuals higher concentrations of MetHb are usually well tolerated, it may endanger oxygen supply in patients with diminished cardiopulmonary reserves or anemia.36 Because of their 2-wavelength technology, conventional pulse oximeters are not able to identify the extent of dyshemoglobinemias.79 The optical analysis of a new pulse CO oximeter (Masimo, Radical 7®)) is based on absorbance measurements at several wavelengths. Consequently, dyshemoglobinemias might also be recorded by a pulse oximeter with sufficient precision. This has been demonstrated in 1 preclinical trial10 and 2 case reports.11,12

This prospective study is the first to evaluate the efficacy of this pulse CO oximeter in a clinical setting. We hypothesized that the results for MetHb are the same for the pulse oximetric method and arterial blood sample measurement using a CO oximeter.


After approval by the ethics committee and written informed consent, we investigated 40 patients, physical status ASA I–III, having orthopedic surgery: 20 patients received an interscalene plexus block with 30 mL prilocaine 1% (i.e., 300 mg) and 20 patients a combined femoral–sciatic nerve blockade with 2 × 30 mL prilocaine 1% (i.e., 600 mg in all). All blocks were performed using a nerve stimulator (Stimuplex HNS 11, Braun, Germany). Injection was only performed if a contraction of indicator muscles could be demonstrated at 0.3 to 0.5 mA (stimulus duration: 0.1 ms).

The pulse CO oximeter Radical 7® is a device manufactured by Masimo Corp. (Irvine, California), which in addition to oxygen saturation (SPO2 in %) can also measure MetHb by pulse oximetry (SpMet%).10 These values could be read using a laptop and stored after conversion into an Excel spreadsheet. The continuous monitoring of patients with the Radical 7® was started before the onset of regional anesthesia.

At the times 0, 15, 30, 60, 120, 180, 240, 300, and 360 minutes after the first injection of prilocaine, 2 mL of arterial blood was taken and immediately analyzed in a blood gas analyzer (ABL-625, Radiometer America, Copenhagen, Denmark) with an integrated CO oximeter as a reference device. The data for MetHb content (cMetHb) and for SAO2 were compared with the corresponding values obtained with the Radical 7®.

For statistical analysis using the Software Package for Social Sciences (SPSS) 15.0 for Windows, we averaged the 9 repeated measurements for each of the 40 patients according to Bland and Altman.13

A probability of P < 0.05 was considered statistically significant.


One patient after interscalene block and 1 patient after combined femoral–sciatic nerve block required general anesthesia for block failure (success rate 95%). Figure 1 shows MetHb levels over time for both types of blocks. Peak levels were reached for interscalene blocks after 120 minutes and for combined femoral–sciatic nerve blocks after 5 hours (Table 1).

Figure 1:
Methemoglobin (MetHb) levels after regional anesthesia with prilocaine: plots show mean MetHb levels after 300 mg prilocaine for interscalene block (ISB) and after 600 mg prilocaine for combined femoral–sciatic nerve block (FSNB).
Table 1:
Methemoglobin Levels and Success Rate After Regional Anesthesia with Prilocaine for Interscalene or Femoral–Sciatic Nerve Blocks

The statistical agreement of the MetHb measurement between the laboratory method as a reference method and the pulse oximetric measurement using the Radical 7® for all 40 patients is shown in Table 2 and Figure 2. According to Bland–Altman analysis (Fig. 2), the bias was 0.27%, and the 95% confidence limits (±1.96 SD) 1.33%. With the increasing rise in MetHb, there is a clear gap between the values reported for functional oxygen saturation by the Radical 7® and the values reported by the CO oximeter in the blood gas analyzer device (Fig. 3). The Radical 7® displays SPO2 readings that run in parallel with and slightly higher than the values for fractional saturation (Fig. 4).

Table 2:
Interclass Statistical Comparison of SpMet (%) Versus cMetHb (%) for Each Subject and for Pooled Data
Figure 2:
Bland and Altman analysis for repeated measurements: bias plot of the difference of pulse-oximeter estimate of methemoglobin (MetHb) (SpMet [%]) and cMetHb% versus the average of SpMet and cMetHb. Averaged data of the 9 repeated measurements. Lines show values of bias (mean of the differences) and ±1.96 SD. cMetHb% = CO-oximeter measurement of methemoglobin.
Figure 3:
Regression analysis: scatter plot of the functional saturation measured by Radical 7® (SPO2) and the functional saturation measured by the CO oximeter (SAO2) versus cMetHb%. Averaged data of the 9 repeated measurements of each of the 40 patients. cMetHb% = CO oximeter measurement of methemoglobin. SEE = SE of the estimate
Figure 4:
Regression analysis: scatter plot of the functional saturation measured by Radical 7® (SPO2) and the fractional saturation measured by the CO oximeter (O2Hb) versus cMetHb%. Averaged data of the 9 repeated measurements of each of the 40 patients. cMetHb% = CO oximeter measurement of methemoglobin. SEE = SE of the estimate


In this prospective study we evaluated a new pulse Co oximeter (Radical 7®, Masimo, Inc.) after regional anesthesia with high doses of prilocaine. We compared the pulse oximetric method for noninvasive monitoring of MetHb with direct arterial measurements by using a reference procedure. A high degree of agreement between the 2 methods could be shown for MetHb values up to 6.6% (mean correlation coefficient = 0.95, bias = 0.27, 95% limits = ±1.33).

In comparison with lidocaine and mepivacaine, prilocaine has the advantage of far less cardiac or central nervous system toxicity.14,15 Nevertheless, prilocaine is not available in much of the world. The presence of acquired methemoglobinemia is often assumed.3,16,17 It is triggered not only by prilocaine but also by many other drugs,3,1821 in particular by benzocaine.17 The symptoms are nonspecific and often unrecognized.3,9 Methemoglobinemia is associated with the reduction in the fractional oxygen saturation. Concentrations <15% are usually well tolerated by healthy individuals, but in patients with anemia or cardiopulmonary diseases, clinical symptoms can occur when the concentration exceeds 8%.3 Despite administration of the recommended threshold dose of prilocaine, it was only possible to assess MetHb values up to 6.6%. Further investigations are necessary to analyze the accuracy of the pulse oximeter at higher levels.

Dyshemoglobinemias cannot be identified by conventional pulse oximeters, because their measurements, based on 2 wavelengths of light absorption, only allow the recording of oxyhemoglobin and desoxyhemoglobin.7,22 The pulse CO oximeter Radical 7® measures the light absorption of 8 different wavelengths. In a preclinical study in healthy volunteers, Barker et al. evaluated a predecessor of the pulse oximeter that we used.10 The results (bias 0%, SD ± 0.45%) differ only slightly from the data presented in our clinical study.

Although the Radical 7®, according to the manufacturer's information, only displays the functional oxygen saturation,23 the data collected for the SPO2 display during the study period tend to follow the fractional rather than the functional oxygen saturation (Figs. 3 and 4). This difference might be a result of the analysis algorithm of the device.

In conclusion, we found a high degree of agreement in measurement of MetHb with a CO oximeter and a noninvasive and readily available pulse-oximetric procedure. This may facilitate early diagnosis and treatment, when necessary, of dyshemoglobinemia.


Financial support for the work: Peter Soeding and Hartmut Gehring are employees of the University Clinic of Schleswig— Holstein, Campus Luebeck, Luebeck, Germany. Device was provided by Masimo, Inc., Germany.


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