Forced-air warming and ultra-clean ventilation do not mix: an investigation of theatre ventilation, patient warming and joint replacement infection in orthopaedics.

We investigated the capacity of patient warming devices to disrupt the ultra-clean airflow system. We compared the effects of two patient warming technologies, forced-air and conductive fabric, on operating theatre ventilation during simulated hip replacement and lumbar spinal procedures using a mannequin as a patient. Infection data were reviewed to determine whether joint infection rates were associated with the type of patient warming device that was used. Neutral-buoyancy detergent bubbles were released adjacent to the mannequin's head and at floor level to assess the movement of non-sterile air into the clean airflow over the surgical site. During simulated hip replacement, bubble counts over the surgical site were greater for forced-air than for conductive fabric warming when the anaesthesia/surgery drape was laid down (p = 0.010) and at half-height (p < 0.001). For lumbar surgery, forced-air warming generated convection currents that mobilised floor air into the surgical site area. Conductive fabric warming had no such effect. A significant increase in deep joint infection, as demonstrated by an elevated infection odds ratio (3.8, p = 0.024), was identified during a period when forced-air warming was used compared to a period when conductive fabric warming was used. Air-free warming is, therefore, recommended over forced-air warming for orthopaedic procedures.

Intraoperative small-dose ketamine does not reduce pain or analgesic consumption during perioperative opioid analgesia in children after tonsillectomy.

OBJECTIVE: Ketamine inhibits the NMDA receptors via non-competitive antagonism, resulting in an antihyperalgesic effect achieved by doses of ketamine much smaller than are required for analgesia. The aim of this study was to determine the extent to which small-dose ketamine, when used in conjunction with remifentanil, has a morphine-sparing effect in the perioperative period. MATERIALS AND METHODS: In this randomized, double-blind, placebo-controlled prospective study, we enrolled 40 children undergoing tonsillectomy. Anesthetic care was standardized. Intraoperative analgesia was provided with remifentanil 0.5 microg x kg(-1) followed by an infusion of 0.25 microg x kg(-1) x min(-1). Group I (ketamine, n = 20) received a bolus dose of ketamine 0.5 mg x kg(-1) followed by a continuous infusion of 2 microg x kg(-1) x min(-1) before start of surgery. The infusion was stopped when surgery ended. Group II (placebo, n=20) received normal saline in the same manner. Pain was assessed postoperatively using the Children's Hospital Eastern Ontario Pain Scale (CHEOPS; range of scores 4 13), and total morphine consumption was recorded in the postanesthesia care unit (PACU). Patients were transferred to the ward and morphine was administered via a patient-controlled analgesia (PCA) device and analgesia was recorded using a visual analogue scale (VAS) (0 - 10). RESULTS: Intraoperative remifentanil consumption was not different between the ketamine group (0.29+/-0.09 microg x kg x min(-1) ) and the control group (0.24+/-0.07 microg x kg x min(-1)). There were no significant differences between CHEOPS scores and VAS score between the two groups. The total mean morphine consumption in the ward was not significantly different between the two groups: 376.5 +/-91.6 microg x kg(-1) with ketamine and 384.4+/-97.3 microg x kg(-1) with placebo. The time-to-first analgesic requirement was also similar in both groups. CONCLUSIONS: Small-dose ketamine did not decrease postoperative pain after tonsillectomy in children when added to a continuous intraoperative remifentanil infusion.

X-linked anhidrotic ectodermal dysplasia with immunodeficiency is caused by impaired NF-kappaB signaling.

The molecular basis of X-linked recessive anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID) has remained elusive. Here we report hypomorphic mutations in the gene IKBKG in 12 males with EDA-ID from 8 kindreds, and 2 patients with a related and hitherto unrecognized syndrome of EDA-ID with osteopetrosis and lymphoedema (OL-EDA-ID). Mutations in the coding region of IKBKG are associated with EDA-ID, and stop codon mutations, with OL-EDA-ID. IKBKG encodes NEMO, the regulatory subunit of the IKK (IkappaB kinase) complex, which is essential for NF-kappaB signaling. Germline loss-of-function mutations in IKBKG are lethal in male fetuses. We show that IKBKG mutations causing OL-EDA-ID and EDA-ID impair but do not abolish NF-kappaB signaling. We also show that the ectodysplasin receptor, DL, triggers NF-kappaB through the NEMO protein, indicating that EDA results from impaired NF-kappaB signaling. Finally, we show that abnormal immunity in OL-EDA-ID patients results from impaired cell responses to lipopolysaccharide, interleukin (IL)-1beta, IL-18, TNFalpha and CD154. We thus report for the first time that impaired but not abolished NF-kappaB signaling in humans results in two related syndromes that associate specific developmental and immunological defects.

Living liver donor surgery: report of initial anesthesia experience.

The charts and anesthetic records of 12 patients who donated the left lateral segment of their liver to a related infant or child to treat liver failure were retrospectively reviewed. Blood loss, need for transfusion, fluids administered, surgical length, and perioperative complications were investigated. The records also were examined to determine the hemodynamic stability of patients undergoing donor hepatectomy to assess their need for invasive monitoring. There were no episodes of hypotension or hemodynamic instability. The average operating time was 9.6 +/- 1.1 hours. The blood loss was 562 +/- 244 mL (range 300 to 1100 mL). Four patients received their own cell saver blood (200 mL, 220 mL, 300 mL, 475 mL), and one patient received 1 U (350 mL) of predonated autologous blood. The average hemoglobin decreased significantly (p = 0.001) from a preoperative value of 14.1 +/- 1.2 to 12.3 +/- 1.8 g/dL in the recovery room. All patients were extubated in the operating room or recovery room. Patients were discharged home in 6.9 +/- 1.3 days (range 5 to 9 days). Living-related liver resection can be performed with noninvasive monitoring and without the need for heterologous blood products.

Perioperative anesthetic management of the kidney-pancreas transplant recipient.

Patients undergoing simultaneous pancreas-kidney transplantation are at risk for a variety of serious perioperative complications. These are related to the chronic and acute problems associated with end-stage renal disease and insulin-dependent diabetes mellitus and the prolonged, vascular and ductal surgery required to implant the two allografts. A number of strategies need to be integrated and diligently implemented to minimize the physiologic perturbations and complications related to the recipient's comorbid conditions and revascularization of the allografts. A major objective of the perioperative anesthetic management of simultaneous pancreas-kidney transplantation is to maximize cardiovascular performance in a way that provides optimum graft perfusion and recovery, while avoiding myocardial ischemia. Adherence to this objective, along with very effective immunosuppressants, surgical refinements, meticulous anesthetic preparation, extensive and frequent physiologic and metabolic monitoring, and quick response to abnormal findings has resulted in remarkably low recipient morbidity and mortality, and very high graft survival rates.

Hemodynamic and metabolic manifestations of acute endotoxin infusion in pigs with and without the malignant hyperthermia mutation.

BACKGROUND: The hypermetabolic state induced by acute endotoxemia and malignant hyperthermia (MH) may be indistinguishable. The aims of this study were (1) to investigate the differences between MH and sepsis, (2) to determine whether acute endotoxemia can trigger MH, and (3) to establish the effects of dantrolene in these two disorders. METHODS: Three groups of swine were studied. All pigs were invasively monitored and initially anesthetized with nontriggering agents. A placebo MH-susceptible group (n = 5) received normal saline whereas the endotoxin groups (MH-susceptible, n = 6; MH-negative, n = 4) received intravenous endotoxin (250 microg/kg total) during 2.5 h. Halothane (1.5%) and succinylcholine (2-4 mg/kg) were then administered, followed by two doses of dantrolene (4 mg/kg total). RESULTS: Endotoxin infusion resulted in pulmonary hypertension and systemic hypotension in pigs with and without the MH mutation, but did not trigger MH. Halothane and succinylcholine triggered MH, evidenced by a markedly higher oxygen consumption in the MH-susceptible pigs that received endotoxin (325+/-196 ml/min) and those that did not (374+/-110 ml/min) compared to the MH-negative pigs (69+/-15 ml/min, P<0.0009), as well as muscular rigidity in the susceptible animals. Dantrolene reversed these changes. Three of the six MH-susceptible pigs that received endotoxin died; two died soon after triggering and one after dantrolene administration. In contrast, none of the MH-negative pigs or the MH-susceptible pigs that did not receive endotoxin died (0 of 9 vs. 3 of 6, P = 0.044). CONCLUSION: Endotoxemia does not trigger MH, but may worsen outcome if it occurs.

Carbon dioxide embolism during laparoscopy: effect of insufflation pressure in pigs.

Carbon dioxide embolism is a rare but potentially devastating complication of laparoscopy. To determine the effects of insufflation pressure on the mortality from carbon dioxide embolism, six swine had intravascular insufflation with carbon dioxide for 30 seconds using a Karl Storz insufflator at a flow rate of 35 mL/kg/min. The initial insufflation pressure was 15 mm Hg. Following recovery from the first embolism, intravascular insufflation using a pressure of 20 mm Hg at the same flow rate was performed in the surviving animals. Significantly less carbon dioxide (8.3 +/- 2.7 versus 16.7 +/- 3.9 mL/kg; p < 0.02) was insufflated intravascularly at 15 mm Hg than at 20 mm Hg pressure. All of the pigs insufflated at 15 mm Hg pressure with a flow rate of 35 mL/kg/min survived. In contrast, 4 of the 5 pigs insufflated at 20 mm Hg pressure died. The surviving pig died when insufflated with 25 mm Hg pressure following an embolism of 15.7 mL/kg. Intravascular injection was often associated with an initial rise in end-tidal carbon dioxide tension, followed by a rapid fall in all cases where the embolism proved fatal. Insufflation should be begun with a low pressure and a slow flow rate to limit the volume of gas embolized in the event of inadvertent venous cannulation. Insufflation should immediately be stopped if a sudden change in end-tidal carbon dioxide tension occurs.

Respiratory foreign bodies and Eikenella corrodens brain abscess in two children.

We report the coexistence of aspirated foreign bodies and brain abscess in two boys. One child had aspirated a metallic needle, and in the other boy partially embedded sunflower seeds were found in the bronchial wall. Both patients had growth of Eikenella corrodens (oral gram-negative flora) from the abscess. Aspirated foreign body in the respiratory tract should be one of the diagnostic considerations if any of the normal oropharyngeal organisms such as E. corrodens is the causative organism of brain abscess.

Differential diagnosis of thyroid crisis and malignant hyperthermia in an anesthetized porcine model.

The intra-operative differential diagnosis between thyroid crisis and malignant hyperthermia can be difficult. Also stress alone can trigger MH. The purposes of this study were: 1) to investigate the metabolic and hemodynamic differences between thyroid crisis and MH, 2) determine how thyroid crisis affects the development of MH, and 3) determine if the stress of thyroid crisis can trigger MH in susceptible individuals. We studied MH susceptible and normal swine. Two groups of animals (MH susceptible and normal) were induced into thyroid crisis (critical core hyperthermia, sustained tachycardia and increase in oxygen consumption) by pretreatment with intraperitoneal triiodothyronine (T3) followed by large hourly intravenous injections of T3. Two similar groups were given intravenous T3 but no pretreatment. These animals did not develop thyroid crisis and served as controls. Thyroid crisis did not result in metabolic changes or rigidity characteristic of an acute episode of MH. When the animals were subsequently challenged with MH triggering agents (halothane plus succinylcholine) dramatic manifestations of fulminant MH episodes (acute serious elevation in exhaled carbon dioxide, arterial CO2, rigidity and acidemia) were noted only in the MH susceptible animals. Although thyroid crisis did not trigger MH in the susceptible animals it did decrease the time to trigger MH (14.1 +/- 7.2 minutes versus 47.2 +/- 17.7 minutes, p < 0.01) in susceptible animals. Hormone induced elevations in temperature and possibly other unidentified factors during thyroid crisis may facilitate the triggering of MH following halothane and succinylcholine challenge.

Total pancreatectomy with islet cell autotransplantation: anesthetic implications.

STUDY OBJECTIVE: To make recommendations for the perioperative management of patients undergoing total pancreatectomy with islet cell autotransplantation. DESIGN: Retrospective review. SETTING: University hospital. PATIENTS: 41 patients undergoing total pancreatectomy with autologous islet cell transplantation for chronic pancreatitis from 1977 to 1996. INTERVENTIONS: The charts and anesthetic records were reviewed, specifically investigating the changes in portal venous pressure, blood pressure (BP), and central venous pressure with islet cell injection. The records also were examined for blood glucose levels, type of fluids administered, blood loss, and postoperative complications. MEASUREMENTS AND MAIN RESULTS: Injection of islet cells into the portal vein caused a significant increase in portal venous pressures (8.5 +/- 4.8 to 27 +/- 16 cm/H2O; p < 0.001), which remained elevated at the end of injection (23 +/- 12 cm/H2O; p < 0.001). Central venous pressures also increased a small amount (9.3 +/- 4.3 to 10.6 +/- 5.8 mmHg; p < 0.05). In contrast, systolic blood pressures (SBPs) fell with administration of the islet cells (110 +/- 15 to 103 +/- 17 mmHg; p < 0.01), but SBP recovered in most patients at the end of injection (106 +/- 16 mmHg; p = NS). However, 6 patients (14.6%) required vasopressors to maintain adequate BPs. Blood glucose levels were significantly higher immediately prior to islet cell infusion in patients who had received dextrose-containing solutions than those who did not (246 +/- 80 vs. 176 +/- 43 gm/dl; p = 0.002). Median blood loss was 2000 ml (range 350 to 12,000 ml), and most patients (95.1%) required blood transfusions. CONCLUSION: Although total pancreatectomy with islet cell autotransplantation is a difficult operation, with significant blood loss, most patients tolerate surgery and injection of islet cells into their portal system without hemodynamic instability. Glucose-containing solutions should not be administered to patients prior to islet cell infusion because hyperglycemia, which can damage islet cells, may result.

Double volume exchange transfusion for ABO incompatible liver transplantation in paediatric patients: intraoperative and preoperative approach.

Double volume blood exchange transfusions (DBVET) were used to reduce the serum antibody levels in six paediatric patients receiving ABO incompatible hepatic allografts. In four patients, the exchange transfusions took place on the ward prior to surgery. In three of these four patients who had titres measured, the anti-A IgM titres fell from 1024 to 64, 64 to 8, and 128 to 16, respectively. The anti-A IgG titres fell from 32 to 16 and 512 to 64 in two patients, but rose from 16 to 32 in the third. In two patients DBVET were performed intraoperatively using a rapid infusion device. The IgM titres fell from 256 to 32 and 64 to 1, respectively, and the IgG titres fell from 16 to 4 and 2 to 0. Intraoperative DBVET can acutely and effectively reduce blood group antibodies. Intraoperative DBVET may reduce graft ischaemia time and allow red blood cell salvage.

Combined liver-total bowel transplantation has no immunologic advantage over total bowel transplantation alone. A prospective study in a porcine model.

BACKGROUND: Rejection remains a major obstacle to successful bowel transplantation in humans. It has been suggested that a simultaneous liver transplant would shield the bowel graft from immunologic attack, but the liver shortage would be aggravated. In a preclinical model, we studied the influence of simultaneous liver grafting by comparing the incidence of early bowel rejection after combined liver-total (small- and large-) bowel transplants vs total bowel transplants alone. METHODS: We assessed the incidence of early post-transplant rejection, graft-vs-host disease, and infection after combined liver-total bowel transplants (group 1, n = 10) and total bowel transplants alone (group 2, n = 9) in outbred Yorkshire Landrace pigs. Liver and bowel grafts were transplanted orthotopically with portal vein drainage after recipient hepatectomy (group 1) and total enterectomy (groups 1 and 2). Posttransplant immunosuppression was performed with intravenous tacrolimus (whole blood levels, 15 to 30 ng/mL) and prednisolone. In groups 1 and 2, bowel biopsy specimens from the ileostomy were obtained daily. In group 1, liver biopsy specimens were obtained weekly. Rejection was graded according to a 4-point scoring system (none, mild, moderate, and severe). RESULTS: Overall graft survival at days 7, 14, and 21 was 89%, 44%, and 11%, respectively, in group 1 vs 100%, 100%, and 86%, respectively, in group 2 (P < .001). Death rates owing to (irreversible) rejection at days 7, 14, and 21 were 0% in groups 1 and 2 (P = .48). Grading of bowel rejection episodes, based on the results of daily biopsy specimens, was not significantly different between the groups whether on individual days or overall. In group 1, the incidence of liver rejection episodes was as high as 66% (day 14 and at autopsy). At autopsy, generalized graft-vs-host disease (skin, native intestine, and native liver) was noted in 55% of group 1 and 43% of group 2 pigs (P = .55). Graft-vs-host disease was noted concurrently with rejection episodes of the liver or bowel grafts. CONCLUSIONS: Simultaneous liver grafting did not further reduce the incidence of early bowel rejection or graft-vs-host disease when compared with total bowel transplants alone. Based on the results of this preclinical study, simultaneous liver grafting is not indicated for patients with short-bowel syndrome and normal liver function.

Thermal response in acute porcine malignant hyperthermia.

This study was designed to evaluate how vital organ and skin-surface temperatures correlate with other clinical signs of a malignant hyperthermia (MH) episode. Six susceptible swine were anesthetized with thiopental and nitrous oxide and kept normothermic (approximately equal to 38 degrees C). After a 30-min control period, halothane (1 minimum alveolar anesthetic concentration) was administered, followed in 5 min by a bolus of succinylcholine (2 mg/kg intravenously). Monitoring included: 1) ETCO2; 2)PaO2, PaCO2, pHa; 3) cardiovascular function; 4) core temperatures (esophagus, pulmonary artery, and rectum); 5) organ temperatures (brain, kidney, liver, and four skeletal muscles); and 6) skin temperatures (forehead, neck, and axilla). Within 10 min after exposure to halothane and succinylcholine, all animals developed fulminant MH. Kidney, liver, and brain temperatures increased more rapidly than pulmonary artery temperature with the onset of MH. Temperatures significantly increased in the visceral organs prior to the detection of contractures within skeletal muscles. The masseter, longissimus dorsi, quadriceps, deltoid, and extensor digiti II intramuscular temperatures were 1-2 degrees C less than pulmonary artery and esophageal temperatures during the episodes, whereas those of the kidney, liver, and brain were the same or slightly greater. When it occurs, core hyperthermia during acute MH results largely from heat produced in central organs, not in skeletal muscle per se. In these swine, changes in axilla skin surface temperatures correlated well with core temperature trends, whereas those of the neck and forehead did not. Unless a skin-surface probe can be placed in close proximity to a major vessel, cutaneous temperatures should not be substituted for measurements at an appropriate core site.

Prior hypothermia attenuates malignant hyperthermia in susceptible swine.

This study was designed to determine the extent by which mild or moderate hyperthermia attenuates the triggering of malignant hypothermia (MH) induced by the combined administration of halothane and succinylcholine. Sixteen susceptible swine were initially anesthetized with nontriggering drugs and then either kept normothermic (approximately equal to 38 degrees C, n = 6) or cooled to induce mild (approximately equal to 35 degrees C, n = 6), or moderate (approximately equal to 33 degrees C, n = 4) hypothermia. Next, after a 30-min control period, the normothermic and mildly hypothermic animals were administered 1 minimum alveolar anesthetic concentration (MAC) halothane followed by a bolus dose of succinylcholine (2 mg/kg). Within 10 min all normothermic animals developed fulminant MH, whereas the onset of MH was slowed or was absent in the mildly hypothermic group. To test whether moderate hypothermia could more effectively minimize the signs of a MH episode, this group of animals was exposed to 1.5 MAC halothane followed 10 min later by a 3-mg/kg bolus of succinylcholine. MH was not induced and anesthesia was then changed to nontriggering drugs (ketamine and pancuronium). The animals were then aggressively rewarmed to 38 degrees C: a slight increase in the ETCO2 was detected, but MH episodes did not spontaneously occur. Subsequently, the readministration of halothane and succinylcholine rapidly provoked fulminant MH. We concluded that the induction of mild hypothermia impairs triggering and reduces the progression of MH induced by the combined administration of halothane and succinylcholine, whereas moderate hypothermia was completely protective and thus could be considered for prophylaxis.

Evaluation of the Augustine Guide for difficult tracheal intubation.

Successful tracheal intubation with Augustine Guide (Augustine Medical, Inc., Eden Prairie, MN) in patients with normal airways has recently been described. There are no studies describing Augustine Guide (AG) use in patients with difficult airways. Accordingly, we studied AG intubation in a population of patients with expected difficult airways due to cervical spine pathology, limited mouth opening, obesity, facial trauma or deformity due to previous operation or radiation and in patients with unexpectedly difficult airways. A total of 44 patients were studied. The AG was used as a primary intubating tool in patients with known difficult airways (n = 36) and as a secondary intubating tool in patients with unexpected inability to intubate using conventional direct laryngoscopy (n = 8). Airway difficulty was predicted by history and physical examination. Intubations were performed under general anaesthesia in 40 of the 44 patients studied. In four patients with predictably difficult airways, topical anaesthesia and sedation were used. Backup methods to achieve intubation were available. Thirty-two of the 36 with known or suspected difficult airways were classified as Mallampati Class III or IV. In the remaining eight patients the preoperative examination suggested an easy airway; however, after induction of general anaesthesia, their laryngeal inlet could not be seen using direct laryngoscopy. Using the AG, all were intubated successfully (36/44 at the first attempt, in 8/44 repositioning of the AG to allow successful laryngeal entry of the stylet was necessary). There were no failures or complications secondary to AG use. This study shows that the AG is a useful device for oral tracheal intubation in patients with known or unexpectedly difficult airways.

Acute transverse myelitis and brainstem encephalitis associated with hepatitis A infection.

A 4-year-old boy became paraplegic during the course of hepatitis A infection. There were significant magnetic resonance imaging changes in the cervical spinal cord and brainstem. The patient's cervical myelopathy resolved entirely after 10 weeks.

Anaesthetic management of bone marrow transplant recipients less than two years of age.

The charts and anaesthetic records of 97 infants less than two years of age who underwent bone marrow transplantation at the University of Minnesota from 1978-1992 were retrospectively reviewed. These infants underwent 564 general anaesthetics. There were 48 perioperative complications, most (39) involving the airway. There were 20 difficult intubations occurring in 13 patients. The causes of the difficult intubations were anatomical abnormalities (12), mucositis (4), pharyngeal oedema (3) and emesis upon induction of anaesthesia (1). Four intraoperative deaths occurred. The deaths were caused by haemorrhage (2), pulmonary embolism (1) and myocardial ischaemia (1). Four patients died within 72 h of surgery; one from cerebral oedema following an intraoperative cardiac arrest, one from fungal septicaemia, one from haemorrhage and one from multiple organ failure following an intracerebral haematoma. Infants undergoing bone marrow transplantation are at high risk for perioperative morbidity and mortality, particularly from complications involving the airway, bleeding or sepsis.

Comparison of the flow rates of central venous catheters designed for rapid transfusion in infants and small children.

Large-bore Hickman catheters are useful in infants and small children for the rapid transfusion of blood or fluids into the central circulation. Recently high-flow plastic sheaths have been developed for the same purpose. We compared the flow rates of normal saline, 5% albumin and packed red blood cells through two sizes of Hickman catheters that have been recommended for major surgery in infants to five sizes of Arrow plastic sheaths of comparable external diameters, and to 14 and 16 gauge Jelco catheters. The flow rates of all three solutions through the plastic sheaths and the 14 gauge Jelco catheters were superior to both sizes of Hickman catheters. Shortening the Hickman catheters improved their flow. High-flow plastic sheaths can provide a useful alternative to Hickman catheters in patients where permanent, large-bore central venous catheters are not required. Hickman catheters should be shortened as much as safely possible if massive haemorrhage is anticipated.

Evidence of venous stasis after abdominal insufflation for laparoscopic cholecystectomy.

Intraoperative venous stasis may increase the risk for perioperative deep vein thrombosis and pulmonary embolism. To determine if abdominal insufflation during laparoscopic cholecystectomy causes venous stasis, eight patients undergoing this procedure had their left common femoral veins examined by a duplex scanner before and after abdominal insufflation; the veins then were examined again before and after deflation. The right femoral veins were catheterized to measure femoral venous pressures. Abdominal insufflation to 14 millimeters of mercury pressure increased femoral venous pressures (10.2 +/- 4.1 millimeters of mercury to 18.2 +/- 5.1 millimeters of mercury; p < 0.001) and slowed peak blood velocities (24.9 +/- 8.5 centimeters per second to 18.5 +/- 4.5 centimeters per second; p < 0.05) without changing the cross-sectional areas (1.1 +/- 0.4 centimeter squared to 1.2 +/- 1.5 centimeter squared; p = NS) of the common femoral veins. Insufflation also reduced or eliminated pulsatility in the common femoral veins in 75 percent of the patients, indicating that insufflation was causing partial proximal venous obstruction. After 80 +/- 21 minutes of surgery, these changes remained significant. Deflation of the abdomen restored normal venous pulsatility in all patients, reduced femoral venous pressures (18.5 +/- 5.2 millimeters of mercury to 12.2 +/- 9.8 millimeters of mercury; p < 0.001), increased the peak blood velocities (14.2 +/- 6.8 centimeters per second to 28.1 +/- 16 centimeters per second; p < 0.05) and decreased the cross-sectional areas (1.4 +/- 0.6 centimeters squared to 0.9 +/- 0.4 centimeters squared; p < 0.05) of the common femoral veins, indicating venous decompression had occurred. The results suggest abdominal insufflation causes venous stasis during laparoscopic cholecystectomies. Measures shown to reduce intraoperative venous stasis, such as pneumatic compressive stockings, may benefit patients undergoing these procedures.

Long-term outcome of Hurler syndrome following bone marrow transplantation.

Previous reports suggested a therapeutic response of lysosomal storage diseases such as Hurler syndrome following bone marrow transplantation. However, a clearer understanding of outcome has awaited long-term follow-up. We evaluated prospectively 11 consecutive patients with Hurler syndrome receiving marrow from an HLA-identical sib donor between September 1983-October 1988. Follow-up evaluations included assessment of donor engraftment by restriction fragment polymorphism analysis, determination of leukocyte alpha-L-iduronidase level, measurement of lumbar cerebrospinal fluid (CSF) pressure, computerized tomography (CT) of the brain, and psychometric testing. In this series there was a survival rate of 9/11 (82%) with all survivors showing complete (7 patients) or partial (2 patients) donor engraftment. Prospective longitudinal evaluation of the 9 surviving children, now 3.8-8.9 years posttransplantation (median 5.5) demonstrated persistence of previously deficient leukocyte alpha-L-iduronidase at levels reflecting the donor genotype and degree of donor engraftment. Urinary glycosaminoglycan excretion declined to near-normal within 5 months of donor engraftment. Prior to treatment, 7 of 8 children studied were found to have occult intracranial hypertension (lumbar CSF pressure > 20 cm CSF); however, all surviving children attained normal or near-normal pressure within 18 months of donor engraftment. Longterm follow-up CT imaging of the brain did not show progressive volume loss (cerebral atrophy) after donor engraftment. Of 9 survivors, 4 children having a developmental quotient (DQ, Mental Development Index on Bayley Scales of Infant Development) above 80 prior to transplantation subsequently maintained IQ scores above this level. However, 5 patients with lower pretransplant DQ scores now have significant cognitive deficits and attention deficit hyperactivity disorder. Progressive brain damage resulting from communicating hydrocephalus may be prevented by successful engraftment. Early transplantation of children with Hurler syndrome who have normal intelligence is likely to have the clearest benefit because long-term intellectual outcome will be limited by brain damage which has occurred prior to treatment.