Analgesia: Brief Report
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.3–6 Because of their 2-wavelength technology, conventional pulse oximeters are not able to identify the extent of dyshemoglobinemias.7–9 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).
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).
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,3,18–21 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.
1. Scott DB, Owen JA, Richmond J. Methaemoglobinaemia due to prilocaine. Lancet 1964;3: 728–9
2. Wright RO, Lewander WJ, Woolf AD. Methemoglobinemia: etiology, pharmacology, and clinical management. Ann Emerg Med 1999;34: 646–56
3. Ash-Bernal R, Wise R, Wright SM. Acquired methemoglobinemia—A retrospective series of 138 cases at 2 teaching hospitals. Med 2004;83: 265–73
4. Bellamy MC, Hopkins PM, Halsall PJ, Ellis FR. A study into incidence of methemoglobinaemia after “three-in-one” block with prilocaine. Anaesthesia 1992;47: 1084–5
5. Knobeloch L, Goldring J, LeMay W, Anderson H. Three cases of methemoglobinemia associated with dental anesthesia. Wis Dent Assoc J 1994;70: 34–5
6. Kreeftenberg HG, Braams R, Nauta P. Methemoglobinemia after low-dose prilocaine in an adult patient receiving barbiturate comedication. Anesth Analg 2007;104: 459–60
7. Reynolds KJ, Palayiwa E, Moyle JT, Sykes MK, Hahn CE. The effect of dyshemoglobins on pulse oximetry: part I. theoretical approach and part II. experimental results using an in vitro test system. J Clin Monit 1993;9: 81–90
8. Barker SJ, Tremper KK, Hyatt J. Effects of methemoglobinemia on pulse oximetry and mixed venous oximetry. Anesthesiology 1989;70: 112–7
9. Yang JJ, Lin N, Lv R, Sun J, Zhao F, Zhang J, Xu JG. Methemoglobinemia misdiagnosed as ruptured ectopic pregnancy. Acta Anesth Scand 2005;49: 586–8
10. Barker SJ, Curry J, Redford D, Morgan S. Measurement of carboxyhemoglobin and methemoglobin by pulse oximetry. Anesthesiology 2006;105: 892–7
11. Annabi EH, Barker SJ. Severe methemoglobinemia detected by pulse oximetry. Anesth Analg 2009;108: 898–9
12. Macknet M, Kimball-Jones P, Applegate R. Benzocaine induced methemoglobinemia after TEE. Resp Care 2007;52: 2007 Open Forum Abstracts [e-abstracts]
13. Bland JM, Altman DG. Agreement between methods of measurement with multiple observations per individual. J Biopharm Stat 2007;17: 571–82
14. Zink W, Graf BM. Toxikologie der Lokalanästhetika. Anaesthesist 2003;52: 1102–23
15. Scott DB, Jerson PJR, Braid DP, Örtengren B, Frisch P. Factors affecting plasma levels of lignocaine and prilocaine. Br J Anaesth 1972;44: 1040–9
16. Weinberg GL. Banning benzocaine: of bananas, bureaucrats, and blue men. Anesth Analg 2009;108: 699–701
17. Guay J. Methemoglobinemia related to local anesthetics: a summary of 242 episodes. Anesth Analg 2009;108: 837–45
18. Anderson ST, Hajduczek J, Barker SJ. Benzocaine-induced methemoglobinemia in an adult. Anesth Analg 1988;67: 1099–101
19. Rehman HU. Methemoglobinemia. West J Med 2001;175: 193–6
20. Fung HT, Lai CH, Wong OF, Lam KK, Kam CW. Two cases of methemoglobinemia following zoplicone ingestion. Clin Toxicol 2008;46: 167–70
21. White CD, Weiss LD. Varying presentations of methemoglobinemia: two cases. J Emerg Med Suppl 1991;1: 45–9
22. Rieder HU, Frei FJ, Zbinden AM, Thomson DA. Pulse oximetry in methaemoglobinaemia. Failure to detect low oxygen saturation. Anaesthesia 1989;44: 326–7
© 2010 International Anesthesia Research Society
23. Radical-7 color display signal extraction pulse co-oximeter with Rainbow Technology. Operator's manual. Irvine, CA: Masimo Corporation, 2007