- Email: [email protected]
Toxic plasma concentration of ropivacaine after a paravertebral block in a patient suffering from severe hypoalbuminemia
Journal of Clinical Anesthesia (2014) 26, 149–151
Case Report
Toxic plasma concentration of ropivacaine after a paravertebral block in a patient suffering from severe hypoalbuminemia☆,☆☆,★ Emile Calenda MD (Consultant Anesthesiologist) a,⁎, Jean Marc Baste MD (Consultant Thoracic Surgeon)b , Ridha Hajjej MD (Consultant Anesthesiologist) a , Eric Danielou MD (Consultant Anesthesiologist) a , Christophe Peillon MD, PhD (Professor; Thoracic Surgeon)b a
Service d'Anesthésie et Réanimation Chirurgicale, Rouen University Hospital, Hôpital Charles-Nicolle, 1 rue de Germont, 76031, Rouen Cedex, France b Service de Chirurgie Thoracique et Cardiovasculaire, Rouen University Hospital, Hôpital Charles-Nicolle, 1 rue de Germont, 76031, Rouen Cedex, France Received 28 February 2013; revised 4 November 2013; accepted 8 November 2013
Keywords: Hypoalbuminemia; Ropivacaine: plasma concentration; Thoracic paravertebral block
Abstract A case of systemic ropivacaine toxicity from a continuous thoracic paravertebral block in an adult patient who received a lobectomy is presented. The catheter was placed by the surgeon. Eleven hours after the start of the infusion, the patient experienced an arrhythmia leading to death. The total venous plasma concentration of ropivacaine was high (3.2 μg/mL). Furthermore, the patient had severe hypoalbuminemia (albumin 24 g/L), which resulted in the increase of the unbound ropivacaine plasma concentration that was responsible for the toxic side effects. © 2014 Elsevier Inc. All rights reserved.
1. Introduction Continuous paravertebral block is commonly recognized as a safe and efficient means of analgesia for thoracic surgery [1]. However, complications of continuous paravertebral ☆
Conflict of Interest: None of the authors has a conflict of interest with the submission. ☆☆ Financial support: No financial support was received for this submission. ★ Informed consent: The family gave oral consent for publication of the report. ⁎ Correspondence: Emile Calenda, MD, Département d’Anesthésie Réanimation, Rouen University Hospital, 1 rue de Germont, 76031 Rouen cedex, France. Tel.: 33 232 888 057; fax: 33 232 888 046. E-mail address: [email protected] (E. Calenda). 0952-8180/$ – see front matter © 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jclinane.2013.11.008
block have been reported [2,3]. These side effects are mechanical and due to a misplaced catheter. Furthermore, a variable resorption of the local anesthetic solution leading to toxic plasma concentration may occur. A case of a systemic toxicity from continuous paravertebral block infused with bupivacaine recently occurred [4]. A case of a severe complication after infusion of ropivacaine in a paraverbral block is presented.
2. Case report A 72 year old old, 70 kg, 182 cm, ASA physical status 3 man was scheduled for superior right lobectomy with
150 videothoracoscopy. Due to a squamous cell carcinoma (epidermoid carcinoma) of the vocal cords with distant tumor in the lung, a hemilaryngectomy followed by radiotherapy had been planned two weeks after the thoracic surgery. No metastasis was found elsewhere. During the surgical procedure, an injury of the pulmonary artery required conversion to open thoracotomy. No decrease in blood pressure (BP) was noticed during this period. At the end of the surgical procedure, a paravertebral catheter was placed in the paravertebral space by the surgeon. After negative aspiration, a bolus of 30 mL of ropivacaine 2 mg/mL (60 mg) was injected through the catheter. After the dressing, a continuous pump infusion was connected to the catheter to deliver a flow of 10 mL/hr of ropivacaine (2 mg/mL). The patient was extubated at the end of the surgical procedure in the operating room (OR). Eleven hours after extubation, with a postoperative oxygen saturation (SpO2) of 96% (with nasal oxygen 3 L/min), the patient lost consciousness and BP severely decreased (systolic blood pressure 50 mmHg). The patient was intubated and external cardiac massage was initiated. Electrocardiogram (ECG) demonstrated a ventricular fibrillation, which alternated with ventricular tachycardia. Several extra thoracic electric shocks were performed. Unfortunately, the resuscitation failed to maintain a regular sinus rhythm and the patient died 45 minutes later.
3. Discussion The preoperative ECG showed a normal sinus rhythm with no signs of heart ischemia or infarction. Lisinopril was interrupted 24 hours before surgery. An autopsy was not performed; it was not possible to definitely exclude a pulmonary embolism (PE). In fact, the main symptom leading to death was a rhythm disturbance; therefore, we assessed the total plasma concentration of ropivacaine in a venous blood sample taken during the arrest, as well as its two carrying molecules. Samples were taken after reintubation and before the first electric shock. Lidocaine was not used; amiodarone (150 mg) was administered after the first electric shock. Samples were collected in heparinized tubes and plasma was separated by centrifugation. Total plasma concentration of ropivacaine was measured by high-performance liquid chromatography. Albumin is not specific, but is the main binding molecule for local anesthetics. Alpha-1-acid glycoprotein (orosomucoid) is specific but is a low carrier. At the time of sampling, the patient had received 140 mL (280 mg 4 mg/kg) of ropivacaine in the paravertebral catheter. Total plasma concentration of ropivacaine was 3.21 μg/mL, albumin 24 g/L (normal N 35 g/L), and orosomucoide 1.15 g/L (normal 0.5-1.5 g/L). Unbound plasmatic concentration of ropivacaine was not assessed. The catheter was intraoperatively
E. Calenda et al. inserted in the paravertebral space by the surgeon just before closing the chest. A bolus of ropivacaine 30 mL (ropivacaine 2 mg/mL - 60 mg - 0.85 mg/kg) was administered. At the end of the protective dressing (30 min later), a 10 mL/hr infusion was connected to the catheter (ropivacaine 2 mg/mL 20 mg/hr - 0.28 mg/kg/hr). By the time the rhythm trouble started, the patient had received 280 mg (4 mg/kg) of ropivacaine over an 11-hour period. There are no reports in the literature of plasma concentrations of ropivacaine after paravertebral block. Nonetheless, we could estimate these concentrations from intercostal blocks [5] or intravenous (IV) infusion [6], even though these sites of administration were not really comparable. Behnke et al administered 5 mL of ropivacaine in 4 intercostal spaces, resulting in a total dose of 20 mL. Groups were divided according to ropivacaine concentration (2 mg/mL, 5 mg/mL, 7.5 mg/mL, and 10 mg/mL). They found that the maximum venous plasma concentration occurred after 11 minutes; the mean and range of total plasma ropivacaine concentration per group were, respectively, 1.3 μg/mL (range: 0.3 - 2.3) in Group 2 mg/mL; 2.1 μg/mL (range: 0.5 - 4.5) in Group 5 mg/mL; 2.4 μg/mL (range: 1.2 - 5.1) in Group 7.5 mg/mL; and 2.5 μg/mL (range: 1.7 - 5.6) in Group 10 mg/mL. They concluded that intercostal blocks were associated with fast absorption of local anesthetics and a high peak of plasma concentration as opposed to other regional anesthesia techniques. Knudsen et al performed an IV infusion of ropivacaine in 12 healthy volunteers and noticed the onset of neurological symptoms at a mean total venous plasma concentration of ropivacaine of 2.2 μg/mL (range: 0.5 3.2). The mean total plasma concentration of ropivacaine found by Behnke et al (2.5 μg/mL) and Knudsen et al (2.2 μg/mL) was lower than the concentration assessed in our patient (3.2 μg/mL). Moreover, the severe hypoalbuminemia (albumin 24 g/L) found in our patient was probably responsible for an increase in unbound ropivacaine concentration that was involved in the clinical side effects. The concentration of 3.2 μg likely would not have led to complications if the albumin concentration had been normal, as Behnke et al reported a plasma peak of 5.6 μg/mL without clinical signs in a patient with a presumably normal concentration of binding molecules. A total plasma concentration of ropivacaine over 2.2 μg/mL was reported as a toxic level by Maurer et al [7]. Despite the availability in each room of several bottles of intralipid, this therapy was not been implemented because the hypothesis of an overdose of local anesthetic was not considered during the resuscitation. The threshold of toxicity of local anesthetics such as ropivacaine is probably decreased in hypoalbuminemic patients, as reported in critically ill hypoalbuminemic patients treated with phenytoin [8]. Takaya et al concluded that when a continuous epidural block was performed in a patient with hypoalbuminemia and low serum cholinesterase activity, blood lidocaine levels might be higher [9].
Toxic ropivacaine concentration in hypoalbuminemia
Acknowledgments We would like to thank Marc Fischler, MD, PhD, Département d'Anesthésie. Hôpital Foch, 40 rue Worth, 92151 Suresnes, France, for his comments. We thank James Bertholle, Rouen University Hospital, Hôpital CharlesNicolle, 1 rue de Germont, 76031, Rouen Cedex, France, for reviewing spelling and grammar.
References [1] Katayama T, Hirai S, Kobayashi R, Hamaishi M, Okada T, Mitsui N. Safety of the paravertebral block in patients ineligible for epidural block undergoing pulmonary resection. Gen Thorac Cardiovasc Surg 2012;60:811-4. [2] Lucas SD, Higdon T, Boezaart AP. Unintended epidural placement of a thoracic paravertebral catheter in a patient with severe chest trauma. Pain Med 2011;12:1284-9.
151 [3] Calenda E, Baste JM, Danielou E, Michelin P. Temporary quadriplegia following continuous thoracic paravertebral block. J Clin Anesth 2012;24:227-30. [4] Fagenholz PJ, Bowler GM, Carnochan FM, Walker WS. Systemic local anaesthetic toxicity from continuous thoracic paravertebral block. Br J Anaesth 2012;109:260-2. [5] Behnke H, Worthmann F, Cornelissen J, Kahl M, Wulf H. Plasma concentration of ropivacaine after intercostal blocks for video-assisted thoracic surgery. Br J Anaesth 2002;89:251-3. [6] Knudsen K, Beckman Suurküla M, Blomberg S, Sjövall J, Edvardsson N. Central nervous and cardiovascular effects of i.v. infusions of ropivacaine, bupivacaine and placebo in volunteers. Br J Anaesth 1997;78:507-14. [7] Maurer K, Blumenthal S, Rentsch KM, Schmid ER. Continuous extrapleural infusion of ropivacaine 0.2% after cardiovascular surgery via the lateral thoracotomy approach. J Cardiothorac Vasc Anesth 2008;22:249-54. [8] Lindow J, Wijdicks EF. Phenytoin toxicity associated with hypoalbuminemia in critically ill patients. Chest 1994;105:602-4. [9] Takaya T, Takiguchi M, Yamasaki Y. Effect of preoperative liver function on serum lidocaine level during continuous epidural block. Masui 1994;43:650-6.
Case Report
Toxic plasma concentration of ropivacaine after a paravertebral block in a patient suffering from severe hypoalbuminemia☆,☆☆,★ Emile Calenda MD (Consultant Anesthesiologist) a,⁎, Jean Marc Baste MD (Consultant Thoracic Surgeon)b , Ridha Hajjej MD (Consultant Anesthesiologist) a , Eric Danielou MD (Consultant Anesthesiologist) a , Christophe Peillon MD, PhD (Professor; Thoracic Surgeon)b a
Service d'Anesthésie et Réanimation Chirurgicale, Rouen University Hospital, Hôpital Charles-Nicolle, 1 rue de Germont, 76031, Rouen Cedex, France b Service de Chirurgie Thoracique et Cardiovasculaire, Rouen University Hospital, Hôpital Charles-Nicolle, 1 rue de Germont, 76031, Rouen Cedex, France Received 28 February 2013; revised 4 November 2013; accepted 8 November 2013
Keywords: Hypoalbuminemia; Ropivacaine: plasma concentration; Thoracic paravertebral block
Abstract A case of systemic ropivacaine toxicity from a continuous thoracic paravertebral block in an adult patient who received a lobectomy is presented. The catheter was placed by the surgeon. Eleven hours after the start of the infusion, the patient experienced an arrhythmia leading to death. The total venous plasma concentration of ropivacaine was high (3.2 μg/mL). Furthermore, the patient had severe hypoalbuminemia (albumin 24 g/L), which resulted in the increase of the unbound ropivacaine plasma concentration that was responsible for the toxic side effects. © 2014 Elsevier Inc. All rights reserved.
1. Introduction Continuous paravertebral block is commonly recognized as a safe and efficient means of analgesia for thoracic surgery [1]. However, complications of continuous paravertebral ☆
Conflict of Interest: None of the authors has a conflict of interest with the submission. ☆☆ Financial support: No financial support was received for this submission. ★ Informed consent: The family gave oral consent for publication of the report. ⁎ Correspondence: Emile Calenda, MD, Département d’Anesthésie Réanimation, Rouen University Hospital, 1 rue de Germont, 76031 Rouen cedex, France. Tel.: 33 232 888 057; fax: 33 232 888 046. E-mail address: [email protected] (E. Calenda). 0952-8180/$ – see front matter © 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jclinane.2013.11.008
block have been reported [2,3]. These side effects are mechanical and due to a misplaced catheter. Furthermore, a variable resorption of the local anesthetic solution leading to toxic plasma concentration may occur. A case of a systemic toxicity from continuous paravertebral block infused with bupivacaine recently occurred [4]. A case of a severe complication after infusion of ropivacaine in a paraverbral block is presented.
2. Case report A 72 year old old, 70 kg, 182 cm, ASA physical status 3 man was scheduled for superior right lobectomy with
150 videothoracoscopy. Due to a squamous cell carcinoma (epidermoid carcinoma) of the vocal cords with distant tumor in the lung, a hemilaryngectomy followed by radiotherapy had been planned two weeks after the thoracic surgery. No metastasis was found elsewhere. During the surgical procedure, an injury of the pulmonary artery required conversion to open thoracotomy. No decrease in blood pressure (BP) was noticed during this period. At the end of the surgical procedure, a paravertebral catheter was placed in the paravertebral space by the surgeon. After negative aspiration, a bolus of 30 mL of ropivacaine 2 mg/mL (60 mg) was injected through the catheter. After the dressing, a continuous pump infusion was connected to the catheter to deliver a flow of 10 mL/hr of ropivacaine (2 mg/mL). The patient was extubated at the end of the surgical procedure in the operating room (OR). Eleven hours after extubation, with a postoperative oxygen saturation (SpO2) of 96% (with nasal oxygen 3 L/min), the patient lost consciousness and BP severely decreased (systolic blood pressure 50 mmHg). The patient was intubated and external cardiac massage was initiated. Electrocardiogram (ECG) demonstrated a ventricular fibrillation, which alternated with ventricular tachycardia. Several extra thoracic electric shocks were performed. Unfortunately, the resuscitation failed to maintain a regular sinus rhythm and the patient died 45 minutes later.
3. Discussion The preoperative ECG showed a normal sinus rhythm with no signs of heart ischemia or infarction. Lisinopril was interrupted 24 hours before surgery. An autopsy was not performed; it was not possible to definitely exclude a pulmonary embolism (PE). In fact, the main symptom leading to death was a rhythm disturbance; therefore, we assessed the total plasma concentration of ropivacaine in a venous blood sample taken during the arrest, as well as its two carrying molecules. Samples were taken after reintubation and before the first electric shock. Lidocaine was not used; amiodarone (150 mg) was administered after the first electric shock. Samples were collected in heparinized tubes and plasma was separated by centrifugation. Total plasma concentration of ropivacaine was measured by high-performance liquid chromatography. Albumin is not specific, but is the main binding molecule for local anesthetics. Alpha-1-acid glycoprotein (orosomucoid) is specific but is a low carrier. At the time of sampling, the patient had received 140 mL (280 mg 4 mg/kg) of ropivacaine in the paravertebral catheter. Total plasma concentration of ropivacaine was 3.21 μg/mL, albumin 24 g/L (normal N 35 g/L), and orosomucoide 1.15 g/L (normal 0.5-1.5 g/L). Unbound plasmatic concentration of ropivacaine was not assessed. The catheter was intraoperatively
E. Calenda et al. inserted in the paravertebral space by the surgeon just before closing the chest. A bolus of ropivacaine 30 mL (ropivacaine 2 mg/mL - 60 mg - 0.85 mg/kg) was administered. At the end of the protective dressing (30 min later), a 10 mL/hr infusion was connected to the catheter (ropivacaine 2 mg/mL 20 mg/hr - 0.28 mg/kg/hr). By the time the rhythm trouble started, the patient had received 280 mg (4 mg/kg) of ropivacaine over an 11-hour period. There are no reports in the literature of plasma concentrations of ropivacaine after paravertebral block. Nonetheless, we could estimate these concentrations from intercostal blocks [5] or intravenous (IV) infusion [6], even though these sites of administration were not really comparable. Behnke et al administered 5 mL of ropivacaine in 4 intercostal spaces, resulting in a total dose of 20 mL. Groups were divided according to ropivacaine concentration (2 mg/mL, 5 mg/mL, 7.5 mg/mL, and 10 mg/mL). They found that the maximum venous plasma concentration occurred after 11 minutes; the mean and range of total plasma ropivacaine concentration per group were, respectively, 1.3 μg/mL (range: 0.3 - 2.3) in Group 2 mg/mL; 2.1 μg/mL (range: 0.5 - 4.5) in Group 5 mg/mL; 2.4 μg/mL (range: 1.2 - 5.1) in Group 7.5 mg/mL; and 2.5 μg/mL (range: 1.7 - 5.6) in Group 10 mg/mL. They concluded that intercostal blocks were associated with fast absorption of local anesthetics and a high peak of plasma concentration as opposed to other regional anesthesia techniques. Knudsen et al performed an IV infusion of ropivacaine in 12 healthy volunteers and noticed the onset of neurological symptoms at a mean total venous plasma concentration of ropivacaine of 2.2 μg/mL (range: 0.5 3.2). The mean total plasma concentration of ropivacaine found by Behnke et al (2.5 μg/mL) and Knudsen et al (2.2 μg/mL) was lower than the concentration assessed in our patient (3.2 μg/mL). Moreover, the severe hypoalbuminemia (albumin 24 g/L) found in our patient was probably responsible for an increase in unbound ropivacaine concentration that was involved in the clinical side effects. The concentration of 3.2 μg likely would not have led to complications if the albumin concentration had been normal, as Behnke et al reported a plasma peak of 5.6 μg/mL without clinical signs in a patient with a presumably normal concentration of binding molecules. A total plasma concentration of ropivacaine over 2.2 μg/mL was reported as a toxic level by Maurer et al [7]. Despite the availability in each room of several bottles of intralipid, this therapy was not been implemented because the hypothesis of an overdose of local anesthetic was not considered during the resuscitation. The threshold of toxicity of local anesthetics such as ropivacaine is probably decreased in hypoalbuminemic patients, as reported in critically ill hypoalbuminemic patients treated with phenytoin [8]. Takaya et al concluded that when a continuous epidural block was performed in a patient with hypoalbuminemia and low serum cholinesterase activity, blood lidocaine levels might be higher [9].
Toxic ropivacaine concentration in hypoalbuminemia
Acknowledgments We would like to thank Marc Fischler, MD, PhD, Département d'Anesthésie. Hôpital Foch, 40 rue Worth, 92151 Suresnes, France, for his comments. We thank James Bertholle, Rouen University Hospital, Hôpital CharlesNicolle, 1 rue de Germont, 76031, Rouen Cedex, France, for reviewing spelling and grammar.
References [1] Katayama T, Hirai S, Kobayashi R, Hamaishi M, Okada T, Mitsui N. Safety of the paravertebral block in patients ineligible for epidural block undergoing pulmonary resection. Gen Thorac Cardiovasc Surg 2012;60:811-4. [2] Lucas SD, Higdon T, Boezaart AP. Unintended epidural placement of a thoracic paravertebral catheter in a patient with severe chest trauma. Pain Med 2011;12:1284-9.
151 [3] Calenda E, Baste JM, Danielou E, Michelin P. Temporary quadriplegia following continuous thoracic paravertebral block. J Clin Anesth 2012;24:227-30. [4] Fagenholz PJ, Bowler GM, Carnochan FM, Walker WS. Systemic local anaesthetic toxicity from continuous thoracic paravertebral block. Br J Anaesth 2012;109:260-2. [5] Behnke H, Worthmann F, Cornelissen J, Kahl M, Wulf H. Plasma concentration of ropivacaine after intercostal blocks for video-assisted thoracic surgery. Br J Anaesth 2002;89:251-3. [6] Knudsen K, Beckman Suurküla M, Blomberg S, Sjövall J, Edvardsson N. Central nervous and cardiovascular effects of i.v. infusions of ropivacaine, bupivacaine and placebo in volunteers. Br J Anaesth 1997;78:507-14. [7] Maurer K, Blumenthal S, Rentsch KM, Schmid ER. Continuous extrapleural infusion of ropivacaine 0.2% after cardiovascular surgery via the lateral thoracotomy approach. J Cardiothorac Vasc Anesth 2008;22:249-54. [8] Lindow J, Wijdicks EF. Phenytoin toxicity associated with hypoalbuminemia in critically ill patients. Chest 1994;105:602-4. [9] Takaya T, Takiguchi M, Yamasaki Y. Effect of preoperative liver function on serum lidocaine level during continuous epidural block. Masui 1994;43:650-6.