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Unexplained Profound Hypoglycemia After Vocal Fold Lipoinjection

Modanlou, Shohreh MD; Marie Giglio, Nicole MS, CRNA; Carroll, Thomas MD; Pancaro, Carlo MD

doi: 10.1213/XAA.0000000000000228
Case Reports: Clinical Care

Vocal fold injection is used for the management of glottal incompetence from various causes. The procedure is well tolerated and has few reported complications. We present a case of a 66-year-old man with long-lasting hoarseness secondary to vocal fold atrophy, who underwent an uneventful bilateral vocal fold injection with autologous fat. While in the recovery area, he experienced profuse sweating approximately 30 minutes after the surgical procedure. His blood glucose value was measured at 24 mg/dL, and plasmatic insulin level was 246 mU/L. To our knowledge, this is the first reported case of a systemic side effect after vocal fold lipoinjection.

From the *Department of Anesthesiology, Tufts Medical Center, Boston, Massachusetts; and Brigham and Women’s Hospital, Boston, Massachusetts.

Accepted for publication May 12, 2015.

Funding: None.

The authors declare no conflicts of interest.

Address correspondence to Shohreh Modanlou, MD, Department of Anesthesiology, Tufts Medical Center, 800 Washington St., Boston, MA 02111. Address e-mail to

Lipoinjection of the true vocal fold (TVF) is a technique used to provide correction to vocal cord paralysis and/or paresis, atrophy, or for any other pathology that may benefit from global TVF augmentation (scar, sulcus vocalis).1,2 Abnormal function of the vocal cords results in incomplete vocal cord closure during voice production. Vocal fold paralysis or paresis may be caused by injury to the head, neck, or chest; from endotracheal intubation of any duration; tumors of the skull base, neck, or chest; viral infections; or through surgical injury to the vagus or recurrent laryngeal nerve.3 Laryngeal nerve paralysis results in an immobile vocal fold with variable position. Symptoms can include hoarseness, inability to phonate, shortness of breath with phonation, a weak cough, and aspiration. Patients with certain neurologic conditions such as multiple sclerosis or who have sustained a stroke may also experience vocal fold paralysis, although in many cases the cause is unknown. TVF atrophy is typically age-related where TVF scar is typically because of aberrant healing from a previous injury, lesion formation, or bleeding. Both can cause significant dysphonia and can be amenable to TVF augmentation.1

The technique of lipoinjection of the TVF used by the laryngologist in this case involves taking a small amount of fat from the abdomen or another fatty subcutaneous area of the body using an open harvest or liposuction technique.4 The fat cells are treated as carefully as possible to not disrupt cell structure. The fat cells are then rinsed in normal saline or Ringer’s lactate solution to remove any fatty acids or blood. The cleaned fat cells are picked manually to remove any further connective tissue or blood. The cleaned fat is then soaked in 100 units of regular insulin for 5 minutes to theoretically stabilize the lipocyte membranes for transfer and improve graft acceptance. The prepared fat is then allowed to dry on a Merocel® sponge before being transferred into an injection syringe for injection into the vocal fold.5,6 It is estimated that between 20% and 90% of the injected fat will develop a blood supply over the next year and remain in the vocal fold.2,5 Lipoinjection of the TVF is designed to permanently medialize the paralyzed vocal cord when the fat is harvested and prepared as described previously and can be used either as a single therapy or in combination with another medialization procedure.2,4,5

Potential complications of lipoinjection include bleeding; infection; reaction to anesthetic; damage to adjacent structures such as the lips, teeth, tongue, and larynx from direct laryngoscopy; hoarseness; airway obstruction; continued dysphagia with aspiration and hematoma; or infection at the abdominal site used for fat harvest.9–12

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Written informed consent was obtained from the patient for publication of this case report.

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A 66-year-old man was scheduled for TVF lipoinjection with autologous fat in the setting of TVF atrophy. His medical history was significant for vocal cord atrophy, paroxysmal atrial fibrillation (AF), and retina melanoma. An IV cannula was placed in the right hand, and 10 mg dexamethasone, 4 mg ondansetron, 0.2 mg glycopyrrolate, and 2 mg midazolam were all given via an IV catheter in the preoperative holding area to prevent postoperative nausea and vomiting, decrease the likelihood of vocal cord edema, and decrease anxiety. The patient was then taken to the operating room and standard American Society of Anesthesiologists monitors were applied before induction. General anesthesia was induced with IV propofol, lidocaine, remifentanil, atracurium, and 100% oxygen. The trachea was intubated with a 5 Mallinckrodt™ (Covidien Ltd., Dublin, Ireland) endotracheal tube, and sevoflurane was delivered at a concentration of 1.0% to 1.2% once proper tube placement was confirmed. A remifentanil continuous infusion was also used throughout the procedure at a dose ranging between 0.15 and 0.2 μg/kg/min. The procedure was performed by the laryngologist as described earlier; however, 2 events occurred that altered this routine protocol. The entire 3-mL vial of regular insulin (100 units/mL) was poured into a cup on the surgical field by the circulating nurse, and the entire 300 units was used to soak the fat instead of the requested 100 units. In addition, the surgical scrub technician loaded the syringes without drying the fat on a Merocel sponge. Thus, the syringes were loaded with fat and an unknown quantity of liquid insulin. The surgeon was handed the fat injection device and was not aware of these deviations from what he had requested to be done. At the conclusion of surgery, after regaining 4 twitches, neuromuscular blockade was antagonized with 2 mg neostigmine and 0.6 mg atropine to avoid residual neuromuscular blockade. Emergence was uneventful, the patient’s trachea was extubated to oxygen via a simple facemask, 0.4 mg hydromorphone was given in the postanesthesia care unit, and the patient maintained hemodynamic stability in the immediate postoperative period. Within 30 minutes in the postanesthesia care unit, the patient became diaphoretic and went into AF. He denied any shortness of breath or chest pain, proceeded to write down the name of his cardiologist, and told us that he felt the same way before when he had episodes of AF. We began to evaluate the patient for a suspected ischemic heart event; chemistry panel, troponin, and CK-MB were drawn, blood glucose was checked, a 12-lead electrocardiogram was obtained, and 10 mg metoprolol was given in divided doses of 5 mg. The bedside blood glucose result was 24 mg/dL, and results were confirmed with a repeat blood sample. Fifty milliliters of IV dextrose 50% was given. A blood glucose level was then checked after dextrose 50% administration, and a repeat result showed 71 mg/dL. Laboratory workup and 12-lead electrocardiogram were both negative for a cardiac etiology but significant for a blood glucose of 21 mg/dL and a plasma insulin level of 246 mU/L. After metoprolol administration, the patient’s heart rate was between 90 and 112 bpm and converted to sinus rhythm in 3 hours. The patient was admitted overnight for cardiac monitoring over the next 24 hours with a cardiology consult. The patient was then discharged home the next day without any further episodes of hypoglycemia or AF.

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There are many differences in technique for fat harvest and preparation before vocal cord injection.1,2,4,5 In our case, the fat harvested from the abdomen was “soaked” in 300 units Humulin R U-100 insulin (Eli Lilly and Co., Indianapolis, IN) solution (100 U/mL) before injection rather than the intended 100 U. Routinely, the fat is allowed to dry on a Merocel sponge and then loaded into the syringe for injection. In this case, it was revealed that the fat was not allowed to dry, thus providing more units of insulin than intended with the injected lipocytes. This case had been performed numerous times by the laryngologist at the institution; however, communication with operating room staff (who were not the usual team for this physician) was overlooked.

Regardless of how many units were added to the dish used to soak the fat in insulin, with this method of fat preparation before injection, the dose of insulin the patient received is unknown. The duration of action of Humulin R U-100 overall is short, but, like with all insulin preparations, is dependent on dose, site of injection, blood supply in relation to site of injection, temperature, and physical activity.7 With systemic absorption, the pharmacologic effect of Humulin R U-100 begins at approximately 30 minutes with a range of 10 to 75 minutes.7 The effect is maximal at approximately 3 hours, although the range is 20 minutes to 7 hours and terminates after approximately 8 hours with a range of 3 to 14 hours.7

The timeframe in which the postoperative hypoglycemic event occurred in addition to the blood glucose levels and serum insulin concentration all confirm our suspicion that the insulin used to soak the fat before injection was significantly absorbed into the systemic circulation. We believe that the hypoglycemia occurring in this case caused physical stress that induced return of a known arrhythmia in this patient. Excess insulin may cause hypoglycemia and hypokalemia, particularly after IV administration. Severe hypoglycemia may cause seizure, coma, or neurologic impairment and may necessitate treatment with intramuscular/subcutaneous glucagon or concentrated IV glucose.7 Sustained carbohydrate intake and observation may also be necessary because hypoglycemia may recur after apparent clinical recovery. Hypokalemia must also be corrected appropriate to each clinical situation.

AF is the most common sustained arrhythmia. Occasionally, AF appears to have a well-defined etiology such as acute hyperthyroidism, an acute vagotonic episode, or acute alcohol intoxication.8 Acute AF is particularly common during the early recovery phase after major vascular, abdominal, and thoracic surgery, in which case autonomic reflexes and/or direct mechanical irritation enhance the arrhythmia.

Acute hypoglycemia causes pronounced physiological responses as a consequence of autonomic activation and results in end-organ stimulation and a profound release of epinephrine. The hemodynamic changes associated with hypoglycemia include an increase in heart rate and peripheral systolic blood pressure, a decrease in central blood pressure, reduced peripheral arterial resistance (causing a widening of pulse pressure), and increased myocardial contractility, stroke volume, and cardiac output.

This case highlights a few potential areas for improvement: all solutions placed onto the surgical field should be included in the “time out” before surgical incision. If insulin is a solution used on the surgical field, the dose should be reviewed as should the amount needed for the actual fat preparation. The anesthesiologist should be intimately involved in the surgical conversation at the time of insulin injection with the lipocytes as they would be for epinephrine, lidocaine, and so on. A protocol should be in place for blood glucose monitoring during clinically appropriate intervals during the case, and the patient should be monitored for systemic effects, if any, postoperatively and have a treatment protocol in place.

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