LipidRescue™ Resuscitation

Use of Intralipid® in an infant with impending cardiovascular collapse due to local anesthetic toxicity
Introduction: We present the first reported case of Intralipid® use in an infant with impending cardiovascular collapse due to local anesthetic toxicity following caudal epidural blockade.
Case Report:
A 40 day old 4.96 kg male baby was scheduled for a right inguinal hernia repair under general anesthesia. Past medical history revealed a full term born baby with complaints of intermittent vomiting and diarrhea since birth. He was not on any medications and had a 24 gauge intravenous access in his right upper extremity. His vital signs in the preoperative holding area included pulse rate of 120 beats/ min, blood pressure of 75/35 mm Hg and oxygen saturation of 99% on room air.
After placement of the standard ASA monitors in the operating room, anesthesia was induced with intravenous glycopyrrolate 50 mcg, propofol 20 mg and rocuronium 3 mg. The trachea was intubated with a 3.5 mm I.D uncuffed endotracheal tube. Following uneventful induction, anesthesia was maintained with 40% oxygen, 60% nitrous oxide and 2% sevoflurane. The baby was then turned to the left lateral position for placement of a caudal epidural block. The sacral hiatus was identified and the caudal epidural space located with a 22 gauge short bevel needle. After negative aspiration for blood and cerebrospinal fluid, 0.5 ml of 0.25% bupivacaine with epinephrine 1:200,000 was injected as a test dose. Following negative test dose, the remaining volume of 3.5 ml of 0.25% bupivacaine with epinephrine was injected in incremental doses over 2-3 minutes. Immediately following completion of the injection of the local anesthetic, the heart rate increased from a baseline of 140 beats/ minutes to 170 beats/ minutes. The ST segment was noted to be elevated 2-3 mm and the T- wave was inverted. The oxygen saturation decreased to 80%, the end tidal carbon dioxide concentration decreased to approximately 20 mm Hg and the blood pressure decreased to 31/ 19 mm Hg. The baby was turned supine, the inhalational anesthetic turned off and the patient ventilated with 100% oxygen. Epinephrine 2 mcg/kg and 20 ml of 5% albumin were given intravenously. The oxygen saturation improved to 100%, but the EKG changes persisted. Epinephrine 2mcg/kg was repeated with no effect. Suspecting local anesthetic toxicity, 10 ml of 20% Intralipid® was given intravenously five minutes after completion of the caudal block. The patient’s hemodynamics rapidly stabilized. A continuous infusion of Intralipid® was ordered, but not started since there were no further changes in the vital signs or the EKG tracing. Anesthesia was resumed with oxygen, nitrous oxide and 2% sevoflurane and the patient monitored closely. After an uneventful observation period of 15 minutes, the surgery commenced. Fentanyl 10 mcg was given intravenously for analgesia. The remainder of the surgical course was smooth and at the completion of surgery, the baby was awakened and the trachea extubated. The failure of the caudal block was further evidenced by absence of apparent sensory and motor blockade in the recovery room.
The patient was observed in the intensive care unit overnight and had no further problems. He was discharged home in stable condition.

Discussion:
In anesthetized children with epidural anesthesia, unintentional intravascular administration of the local anesthetic occurs in less than 1% of cases (1). Current suggested criteria for a positive test dose in anesthetized children include HR increase > 10 beats per minute, systolic blood pressure increase > 15 mmHg, and an increase in T wave amplitude > 25% in lead II (2). It has been reported that accidental intravascular injection could occur after a negative aspiration test for blood in caudal epidural blocks (3, 4). Incremental injection of local anesthetic while closely monitoring the EKG and the vital signs has been recommended to prevent local anesthetic toxicity due to inadvertent systemic injection. In fact, in his review article on local anesthetic toxicity, Tobias suggested that the test dose should be administered incrementally in 0.1–0.2 mL/kg aliquots with an observation time of 60–90 s after each injection (2). However, this would require taking up to 10-15 minutes for injecting the total local anesthetic dose and may not be practical in most clinical scenarios.
Bupivacaine has been widely used for years and is still the most popular local anesthetic for caudal epidural blockade in children (5). Cardiac arrest resistant to resuscitation following systemic toxicity and a prolonged effect on the cardiac conduction system are drawbacks of bupivacaine (6). Infants are at greater risk of bupivacaine toxicity because the level of [alpha] 1-acid glycoprotein, which binds bupivacaine, is decreased in infants compared with older age groups (7). The recommended safe dose of bupivacaine for caudal epidural blockade in infants is 2.5 mg/kg (8). Newer local anesthetic agents such as levobupivacaine and ropivacaine may provide comparable caudal analgesia with reduced cardiac and central nervous system toxicity (9). However levobupivacaine is no longer available in USA as Purdue Pharma® discontinued its levobupivacaine injection because its rights to manufacture or distribute the product expired. Celltech® owns the rights to the product but has no plans to manufacture or distribute levobupivacaine injection (American Society of Health- Pharmacists® website). Ropivacaine in contrast to bupivacaine has local vasoconstricting properties and is not available pre-mixed with epinepherine in commercially available injections. There are conflicting reports regarding the advisability and effectiveness of adding epinepherine to ropivacaine for epidural injection (10, 11).
The exact mechanism of lipid emulsion reversal of local anesthetic toxicity is unclear. It is proposed that bupivacaine partitions preferentially into lipid globules and a “lipid sink” is created decreasing cardiac bupivacaine concentrations after lipid infusion (12). The other alternative theory is a possible positive metabolic effect of lipid infusion (13). It has been suggested that local anesthetics inhibit mitochondrial carnitine- acylcarnitine translocase and elevated triglyceride levels provide an important energy source for the myocardium (14).
The rapid appearance of cardiovascular depressant effect of the local anesthetic agent in our case likely points to an intravascular or intraosseous injection rather than rapid absorption as the probable cause. It is possible that partial intravascular injection might have contributed to lesser severity of the symptoms as opposed to complete cardiovascular collapse. It is also likely that prompt use of Intralipid® on our part might have prevented this exact scenario. Differential diagnosis of cardiac arrest like hypoxia, anesthetic overdose, anaphylactic reaction and pneumothorax were considered, but thought unlikely due to absence of other clinical signs and the timeline of events. Cardiopulmonary resuscitation should always begin with ABCs- airway, breathing and cardiovascular support. However, in case with high index of suspicion of local anesthetic toxicity due to inadvertent systemic injection, we highly recommend the early use of Intralipid® or any other lipid emulsion.


References:
1. Cladis, Franklyn P, Litman, Ronald S. Transient Cardiovascular Toxicity with Unintentional Intravascular Injection of 3% 2-Chloroprocaine in a 2-month-old Infant. Anesthesiology: 100(1). 2004; 181-3
2. Tobias JD. Caudal epidural block: a review of test dosing and recognition of systemic injection in children. Anesth Analg 2001; 93:1156–61.
3. Prentiss JE. Cardiac arrest following caudal anesthesia. Anesthesiology1979; 50:51-3.
4. Schweitzer SA. Avoiding intravascular injections during epidural anesthesia. Anesthesiology 1980; 53:81.
5. Tsui, Ban CH, Berde, Charles B. Caudal analgesia and anesthesia techniques in children. Current Opinion in Anaesthesiology. 2005; 18(3):283-8.
6. Clarkson CW, Hondeghem LM. Mechanism for bupivacaine depression of cardiac conduction: fast block of sodium channels during the action potential with slow recovery from block during diastole. Anesthesiology 1985; 62:396–405.
7. Mazoit JX, Denson DD, Samii K. Pharmacokinetics of bupivacaine following caudal anesthesia in infants. Anesthesiology 1988; 68:387–91.
8. Tetsu Uejima, MD, and Santhanam Suresh, MD. Is 0.375% Bupivacaine Safe in Caudal Anesthesia in Neonates and Young Infants? Anesth Analg 2002; 94:1041
9. Tsui, Ban CH, Berde, Charles B. Caudal analgesia and anesthesia techniques in children. Current Opinion in Anesthesiology. 2005; 18(3): 283-8.
10. Lee BB, Ngan Kee WD, Plummer JL, Karmakar MK, Wong AS. The effect of the addition of epinephrine on early systemic absorption of epidural ropivacaine in humans. Anesth Analg. 2002 ; 95 (5):1402-7
11. Ngan Kee WD, Khaw KS, Lee BB, Wong EL, Liu JY. The limitations of ropivacaine with epinephrine as an epidural test dose in parturients. Anesth Analg. 2001 ; 92 (6):1529-31
12. Weinberg GL, Ripper R, Murphy P, Edelman LB, Hoffman W, Strichartz G, Feinstein DL. Lipid infusion accelerates removal of bupivacaine and recovery from bupivacaine toxicity in the isolated rat heart. Reg Anesth Pain Med 2006; 31: 296–303
13. Stehr SN, Ziegeler JC, Pexa A, Oertel R, Deussen A, Koch T, Hubler M. The effects of lipid infusion on myocardial function and bioenergetics in l-bupivacaine toxicity in the isolated rat heart. Anesth Analg 2007;104:186–92
14. Wildsmith J.A.W. Treatment of local anaesthetic toxicity. Anaesthesia, 2008, 63 778-89.

I see this case has now been published:

J Anesth 2009;23:439-441

Great!

seems to be a blog for professionals and amateurs but they learn