Anesthesia considerations for patients with de Barsy syndrome

Anesthesia considerations for patients with de Barsy syndrome

Journal of Clinical Anesthesia (2010) 22, 499–504 Original contribution Anesthesia considerations for patients with de Barsy syndrome☆,☆☆ Elisabeth ...

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Journal of Clinical Anesthesia (2010) 22, 499–504

Original contribution

Anesthesia considerations for patients with de Barsy syndrome☆,☆☆ Elisabeth P. Aponte MD (Resident), Hugh M. Smith MD, PhD (Assistant Professor)⁎, Bryan J. Wanek CRNA, MNA (Certified Registered Nurse-Anesthetist), Steven R. Rettke MD (Professor of Anesthesiology) Department of Anesthesiology, Mayo Clinic College of Medicine, 200 First St., SW, Rochester, MN 55905 Received 16 November 2008; revised 24 December 2009; accepted 4 January 2010

Keywords: Anesthesia; de Barsy syndrome; nonmalignant hyperthermia

Abstract Study Objective: To determine anesthetic considerations for patients with de Barsy syndrome, a rare complex whose hallmark findings include cutis laxa, progeria, and multiple orthopedic and ophthalmologic abnormalities. Design: Retrospective chart review. Setting: Medical center. Measurements: A search of Mayo Clinic medical records from 1968 to 2007 identified two patients with de Barsy syndrome who underwent a combined total of 35 anesthetics for diagnostic and surgical procedures. Data collected included: age, gender, ASA physical status, relevant comorbidities, surgical procedures, airway management, vascular access, monitoring, anesthetic induction, maintenance, and other observations. Main Results: A wide range of anesthetics and techniques were used. Apart from 4 episodes of intraoperative hyperthermia and postoperative tachycardia, no complications were noted. These episodes may be similar to the nonmalignant hyperthermia reported in osteogenesis imperfecta and Costello syndrome patients. Conclusions: While the safety of any anesthetic technique cannot be established or extrapolated from a small series, given the extreme rarity of the syndrome, these cases suggest the relative safety of anesthesia in de Barsy syndrome patients. © 2010 Elsevier Inc. All rights reserved.

1. Introduction

☆ Supported by the Department of Anesthesiology, Mayo Clinic, Rochester, MN only. ☆☆ The authors have no conflicts of interest to disclose. ⁎ Corresponding author. Tel.: +1 (507) 284 9700; fax: +1 (507) 284 0120. E-mail address: [email protected] (H.M. Smith).

0952-8180/$ – see front matter © 2010 Elsevier Inc. All rights reserved. doi:10.1016/j.jclinane.2010.01.004

First described in 1968, de Barsy syndrome consists of cutis laxity, progeroid aspect, corneal clouding, severe myopia, cataract, characteristic facies, growth and mental retardation, athetoid movements, and multiple orthopedic manifestations [1-11]. To date, 30 patients have been reported with the condition [12]. Patients with de Barsy syndrome frequently need diagnostic and surgical procedures requiring


E.P. Aponte et al.

anesthesia. However, evaluation of anesthetic techniques, special considerations, and outcomes in de Barsy syndrome patients have not been described in the medical literature.

2. Materials and methods After receiving study approval from the Mayo Clinic Institutional Review Board (Rochester, MN, USA), the medical records between the years 1968 and 2007 were searched for patients with de Barsy syndrome. Since a single, comprehensive medical index system does not exist that spans the time frame from the first description of de Barsy syndrome to the present, several databases were queried. An electronic text keyword search of the Berkson Medical and Surgical Indexing System was conducted for the years 1968 through 1975. An electronic keyword search of the Mayo Clinic Life Science System database (introduced in 1996) was conducted for the years 1996 through 2007. The Hospital International Classification of Diseases Adapted (HICDA) Code for de Barsy syndrome was established in 1995, and the Mayo Clinic Medical Index was searched from 1995 to 2007. In addition, because both cutis laxa and progeroid aspect are key elements of de Barsy syndrome, HICDA codes were searched from 1976 to 2007 to identify possible de Barsy syndrome patients coded as one of these two disease states. No exclusionary criteria were applied. The anesthetic and surgical records of de Barsy syndrome patients were analyzed. Data collected included age, gender, ASA physical status, relevant comorbid conditions, surgical procedure, airway management, vascular access, monitoring, anesthetic induction, maintenance, intravenous (IV) and oral analgesics, muscle relaxants, antibiotics, and blood product transfusions. Clinical observations pertaining to the anesthetics were recorded.

3. Results Two patients with de Barsy syndrome were identified, a man and a woman. The male patient had multiple congenital anomalies, including cutis laxa, bilateral cataracts, dislocated hips, generalized hypotonia, bilateral hand deformities, microcephaly, small size for gestational age, depressed nasal bridge, prominent helices, short proximal long bones, short thorax, hypoplastic scrotum, undescended testes, bilateral inguinal hernia, and talipes varus. It was also noted during an endoscopy that the tracheal mucosa was friable, suggesting extension of cutis laxa (Fig. 1). Between 10 months and 8 years of age, he underwent 26 anesthetics for diagnostic and surgical procedures such as cataract extractions, derotational osteotomy, capsulodesis of thumbs, ear tube placement, and Nissen fundoplication. The most extensive surgery involved a thoracotomy and repair of double aortic arch by vascular ring division (Table 1).

Fig. 1 Endoscopy of trachea of boy with de Barsy syndrome showing friable mucosa suggesting extension of cutis laxa to the trachea.

Clinical findings for the female patient included cutis laxa (Fig. 2), progeroid aspect, bilateral teratologic hip dislocation, facial dysmorphism, bilateral hand and talus deformities, failure to thrive, and developmental delay. Between the ages of one and 12 years, she underwent 9 anesthetics for corrective surgeries such as open reduction with capsulorrhaphy and femoral shortening (Table 2). The two patients underwent a combined total of 35 anesthetics, including 21 general anesthetics and 14 episodes of monitored anesthesia care. Two regional anesthetics were performed for postoperative pain management. One regional anesthetic was a caudal block following bilateral femoral synthes; the other was an axillary brachial plexus block preceding right thumb capsulodesis. For all the operations, both patients were listed as ASA physical classification status II or III. The male patient was classified as ASA physical status III in 80% of cases and ASA physical status II in the remaining 20%. Conversely, the female patient was classified as ASA physical status III in 37% of cases and ASA physical status II in the remaining 63%. The most significant preoperative conditions included patent foramen ovale, atrial septal defect, double aortic arch, asthma, and severe gastroesophageal reflux disease requiring Nissen fundoplication. Other comorbidities included musculoskeletal deformities, especially in the hands, microcephaly, hypotonia, and mental retardation.

Anesthesia and de Barsy syndrome Table 1


Male patient: surgical and diagnostic procedures

Date of surgery (mm/dd/yy)

Age at surgery (mos-yrs)


Type of anesthesia

Duration (min)

01/16/98 ⁎ 01/19/98 ⁎ 01/26/98 02/12/98 † 03/30/98 02/19/99 †, ‡

10 10 10 11 1 1

General General MAC General General General

126 112 43 360 110 300

03/17/99 03/24/99 06/18/99 †, ‡

2 2 2

MAC MAC General

N/D 60 238

06/28/99 07/13/99 07/16/99 § 02/16/01 02/26/01 03/01/01 †

2 2 2 4 4 4

MAC MAC MAC General General General

N/D 57 35 159 62 205

03/23/01 05/07/01 08/08/01 05/25/01 † 07/29/03 08/18/03 † 07/12/05 07/29/05 †, || 08/24/05 †

4 4 4 4 6 6 8 8 8

MAC General MAC General MAC General MAC General General

25 91 40 210 33 52 35 122 172

09/06/05 † 09/26/05

8 8

Right cataract extraction Left cataract extraction Examination of eyes Left hip arthrogram and open reduction. Skin biopsy Examination and bilateral medial rectus recession Left thumb MCP joint stabilization with tendon transfer, excision of delta phalynx, and hardware removal Dressing removal Kirschner wire removal Right thumb MCP joint stabilization with tendon transfer, web space deepening, and groin split-thickness skin graft Examination, right thumb Wound check, splint fabrication Eye examination Magnetic resonance imaging, chest Eye examination Laparoscopic Nissen fundoplication, percutaneous endoscopic gastrostomy tube placement Percutaneous endoscopic gastrostomy removal Bilateral myringotomy and tube placement; odontectomy Eye examination Left thoracotomy for vascular ring division Eye examination Esophagogastroduodenoscopy Eye examination Capsulodesis right thumb Bilateral orchiopexy, circumcision, esophagogastroduodenoscopy, triple site biopsies Eye examination Kirschner wire removal

MAC General

34 178


MAC = monitored anesthesia care, MCP = metacarpophalangeal, N/D = not documented. ⁎ Intraoperative fever. † Forced-air warmer. ‡ Intraoperative fever and postoperative tachycardia. § Postoperative tachycardia. || Brachial plexus block with bupivacaine.

A variety of IV and volatile anesthetic agents were used. Propofol was used for induction in 5 of 35 (14%) anesthetics and thiopental sodium was used in two of 35 (5.7%) cases. All other general anesthetics commenced by inhalation induction with sevoflurane or halothane. Laryngeal Mask Airways were placed without difficulty during 5 anesthetics. Endotracheal intubation was performed in 20 of 35 (57%) cases. On a Mayo Clinic airway difficulty assessment scale (0 – 2, with 0 = easy and 2 = extremely difficult airway), all intubations were rated “0” except for one intubation, rated “1”. This intubation was performed in preparation for an eye examination and involved a size 4 endotracheal tube. The laryngoscopist noted “thickened anterior larynx vocal cords.” Anesthesia was maintained with isoflurane in 7 of 35 (20%) anesthetics, with sevoflurane in 14 of 35 (40%) and with halothane in one of 35 (b 3%) cases. All other anesthetics were maintained with a combination of these three gases. Nitrous oxide was used in 21 of 35 (60%) cases.

Fentanyl was the most commonly used opioid in 14 of 35 (40%) anesthetics, with an average cumulative dose of 56 lg. Regional blocks with bupivacaine were performed for postoperative pain control in two cases. One of the anesthetics included succinylcholine combined with cisatracurium. All others used vecuronium in 6 of 35 (17%), atracurium in 6 of 35 (17%), pancuronium in one of 35 (3%), and cisatracurium in two of 35 (6%) anesthetics. Adjuvant drugs included ondansetron, lidocaine, atropine, neostigmine, acetaminophen, midazolam, and clonidine (Tables 3 and 4). Special monitoring included three arterial and one central catheter [right internal jugular vein (RIJV)]. Two 24-gauge (G) arterial catheters were placed in the radial artery. During a thoracotomy for vascular ring division, RIJV and 22-G femoral arterial catheters were placed. No difficulty or complication was reported during or after vascular access procedures. Information regarding cushioning and positioning was not available.


E.P. Aponte et al. Table 3

Anesthetic agents


Anesthetic agents


Thiopental sodium Propofol Sevoflurane Isoflurane Sevoflurane followed by isoflurane Halothane Maintenance Isoflurane Sevoflurane Halothane Nitrous oxide Analgesia Fentanyl Morphine Oxymorphone Regional block with bupivacaine

Usage Average (%) dose

Dose (per kg)

5.71% 25 mg

4 mg/kg

14.3% 60.0% 2.85% 8.57%

17 mg N/A N/A N/A

2 mg/kg N/A N/A N/A

20.0% 20.0% 40.0% 2.85% 60.0% 40.0% 2.85% 8.57% 5.55%

N/A N/A N/A N/A N/A 56 lg 0.65 mg 0.075 mg N/A

N/A N/A N/A N/A N/A 7 lg/kg 0.1 mg/kg 0.013 mg/kg N/A

N/A = not applicable.

Fig. 2 Lower extremities of female with de Barsy syndrome showing cutis laxa and foot deformities.

3.1. Outcomes of anesthetics Intraoperative hyperthermia occurred during 4 of the 26 anesthetics in the male patient. The maximum temperatures were 38.7°C, 39.3°C, 38.2°C, and 39.4°C. All temperature elevations occurred during general anesthesia lasting 112

Table 2

minutes or longer. Two hyperthermic episodes were followed by postoperative tachycardia. Hyperthermia was not associated with increases in end-tidal CO2 (ETCO2) and dantrolene was not required. Other than tachycardia, no other hemodynamic disturbances were noted. Forced-air warmers were used during two of the 4 anesthetics with intraoperative fever. Forced-air warmers or warm blankets were also used in 7 of the 22 uneventful anesthetics. Case data from the 4 episodes of intraoperative hyperthermia are summarized in Table 5.

Female patient: surgical and diagnostic procedures

Date of surgery (mm/dd/yy)

Age (mos-yrs)

10/11/93 ⁎


10/26/93 11/09/93 11/22/93 12/03/93 12/06/93 04/21/95 04/17/03 ⁎

1 1 1 1 1 3 10

04/21/03 01/16/05 ⁎

10 12


Type of anesthesia

Duration (min)

Left hand manipulation, open reduction of left hip, left proximal femoral shortening Cast change Cast change Removal of spica cast and arm cast Right hip open reduction, right proximal femoral shortening Manipulation of hand and cast application Foreign body removal, bilateral femoral synthes Bilateral hamstring lengthening and patellar tendon imbrication Wound check and bilateral long leg casts Left distal tibia derotation osteotomy



MAC MAC General General MAC General † General

70 N/D 150 405 135 250 333

N/D General

N/D 180

MAC = monitored anesthesia care, N/D = not documented. ⁎ Forced-air warmer. † Caudal block with bupivacaine.

Anesthesia and de Barsy syndrome Table 4


Adjuvant drugs

Muscle relaxants

Adjuvant drugs



Usage (%)

Average dose

Dose (per kg)

Succinylcholine Vecuronium Atracurium Cisatracurium Pancuronium Ondansetron Lidocaine Atropine Neostigmine Glycopyrrolate Midazolam Tylenol Clonidine Cefazolin (Ancef) Gentamicin

2.85% 17.1% 17.1% 5.71% 2.85% 14.3% 5.71% 20.0% 17.1% 14.3% 2.85% 8.57% 2.85% 28.6% 2.85%

6 mg 1 mg 3 mg 0.6 mg 2.9 mg 1 mg 11 mg 0.16 mg 0.35 mg 0.2 mg 1 mg 256 mg 2.6 lg 425 mg 13 mg

0.9 mg/kg 0.2 mg/kg 1 mg/kg 0.09 mg/kg 0.3 mg/kg 0.02 mg/kg 1.8 mg/kg 0.09 mg/kg 0.08 mg/kg 0.04 mg/kg 0.1 mg/kg 41.9 mg/kg 0.2 lg/kg 40.8 mg/kg 1.6 mg/kg

4. Discussion Given the wide array of congenital abnormalities requiring surgical intervention, anesthesiologists in several subspecialties (eg, cardiac, pediatric) may be required to care for these patients. The progeroid characteristics of these patients may place them at greater risk for advanced physiological age resulting in heart failure with myocardial fibrosis, atherosclerotic heart disease, and angina [13]. While many aspects of de Barsy syndrome such as cutis laxa, progeria, mental retardation, and hypotonia would suggest conditions associ-

Table 5

ated with anesthetic difficulties, other than hyperthermia this series did not find any unanticipated problems. The episodes of intraoperative fever and postoperative tachycardia raised the concern of predisposition to malignant hyperthermia (MH). While the etiology of the hyperthermia remains unclear, suspicion of MH is low since temperature elevations were not associated with muscle rigidity, disturbance of ETCO2, or hemodynamic compromise. The anesthesia records indicated tachycardia in the setting of hyperthermia, but no mention of “malignant hyperthermia” was evident. In addition, no laboratory test was performed to

Intraoperative hyperthermia and tachycardia

Date Procedure

Hyperthermia episode #1

Hyperthermia episode #2

Hyperthermia episode #3 and postoperative tachycardia

Hyperthermia episode #4 and postoperative tachycardia

1/16/1998 Right cataract extraction

1/19/1998 Left cataract extraction

2/19/1999 ⁎ Left thumb MCP joint stabilization with tendon transfer 38.2°C 300 Inhalation induction with sevoflurane Sevoflurane and halothane

6/18/1999 ⁎ Right thumb MCP joint stabilization with tendon transfer 39.4°C 238 Inhalation induction with sevoflurane Isoflurane, sevoflurane, and N2O Fentanyl (24 lg)

Maximal temperature (°C) 38.7°C Duration of anesthesia (min) 126 Induction Inhalation induction with sevoflurane Maintenance Isoflurane and N2O

39.3°C 112 Inhalation induction with sevoflurane Isoflurane and N2O




Muscle relaxants

Atracurium (2 mg)

Atracurium (2.5 mg)

Adjuvant drugs

None Ondansetron (0.5 mg) Neostigmine (0.25 mg) Glycopyrrolate (0.25 mg) Tylenol (325 mg) None None Cefazolin (Ancef) (300 mg) None


MCP = metacarpophalangeal, N2O = nitrous oxide. ⁎ Forced-air warmer.

Fentanyl (6 lg) and oxymorphone (0.075 mg) Succinylcholine (6 mg) and cisatracurium (0.6 mg) None

Cisatracurium (0.6 mg)

504 investigate the condition. The suspicion of MH was further lowered by the absence of family history of MH and the resolution of all episodes of hyperthermia without the use of dantrolene. It is unknown if the hyperthermia was specific to this patient or whether other de Barsy syndrome patients may be affected, as in other congenital syndromes. Nonmalignant hyperthermia has been reported in other congenital syndromes such as osteogenesis imperfecta and Costello syndrome [14,15]. It has also been described in patients undergoing bidirectional Glenn procedures and protracted eye operations involving high atropinization [16,17]. Other more well known etiologies for non-malignant hyperthermia include neuroleptic malignant syndrome, anticholinergic drugs, allergic drug reactions, infections or sepsis, warm environments, prolonged general anesthesia, hypovolemia, pheochromocytoma, thyrotoxicosis, and other neuroendocrine disorders [16,17]. Of the known etiologies of non-malignant hyperthermia, iatrogenic over-warming and prolonged general anesthesia were possible explanations in this case. The mean anesthesia duration for the 4 episodes of hyperthermia was 194 minutes compared with an average of 113 minutes for all other cases. Hyperthermia occurred in two ophthalmologic procedures and two peripheral hand procedures–procedures in which environmental fevers are extremely common. This situation may represent a likely explanation for the fevers, especially where a normal ETCO2 was noted. In shorter procedures, in which more exposure to ambient air was likely, fevers were not seen. While longer duration of anesthesia may have contributed to the development of hyperthermia, other unknown etiologies also may have been involved since some of the uneventful anesthetics were longer than those associated with hyperthermia. While an iatrogenic etiology is a possible explanation, the repeated occurrence of hyperthermia in the same patient suggests an unknown etiology or possible underlying metabolic disorder similar to that of osteogenesis imperfecta and Costello syndrome patients. Interestingly, in two case reports of intraoperative hyperthermia in patients with Costello syndrome, isoflurane was used in one and sevoflurane in the other [14,18]. In our review, sevoflurane was the only anesthetic agent or adjuvant found in common with all 4 cases of hyperthermia. Although the genetic cause of de Barsy syndrome is unknown, its mode of inheritance is thought to be autosomal recessive [12]. The proposed pathogenesis has been the effect of elastin deficiency on the function of many genes, leading to multisystemic symptoms ranging from progeria to mental retardation [2]. Cutis laxa, Williams syndrome, and non-syndromic supravalvular aortic stenosis are other disorders associated with elastin deficiencies [19]. In patients with cutis laxa, anesthetic management must include cardiac and pulmonary evaluations to rule out aortic aneurysm and pulmonary emphysema. Considerations for cutis laxa include difficult vascular access due to abnormal skin and avoidance of increases in pulmonary artery (PA) pressure and maintenance of inotropy, to prevent – or not worsen – PA hypertension or cor pulmonale. Specifically, in cutis laxa

E.P. Aponte et al. patients with emphysema or PA hypertension, nitrous oxide should be avoided [20]. The safety of any anesthetic technique cannot be established or extrapolated from two patients. Standard IV agents including induction drugs, opioids, local anesthetics, muscle relaxants, antibiotics, and antiemetics were used in 35 anesthetics without incident. Similarly, inhalation induction and inhalation agents did not produce any notable untoward events. Vigilance and appropriate steps to maintain normothermia are prudent, but avoidance of MH-triggering agents is not supported by the evidence at this time.

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