Role of epigenetic mechanisms in transmitting the effects of neonatal sevoflurane exposure to the next generation of male, but not female, rats.

BACKGROUND: Clinical studies report learning disabilities and attention-deficit/hyperactivity disorders in those exposed to general anaesthesia early in life. Rats, primarily males, exposed to GABAergic anaesthetics as neonates exhibit behavioural abnormalities, exacerbated responses to stress, and reduced expression of hypothalamic K+-2Cl- Cl- exporter (Kcc2). The latter is implicated in development of psychiatric disorders, including male predominant autism spectrum disorders. We tested whether parental early life exposure to sevoflurane, the most frequently used anaesthetic in paediatrics, affects the next generation of unexposed rats. METHODS: Offspring (F1) of unexposed or exposed to sevoflurane on postnatal day 5 Sprague-Dawley rats (F0) were subjected to behavioural and brain gene expression evaluations. RESULTS: Male, but not female, progeny of sevoflurane-exposed parents exhibited abnormalities in behavioural testing and Kcc2 expression. Male F1 rats of both exposed parents exhibited impaired spatial memory and expression of hippocampal and hypothalamic Kcc2. Offspring of only exposed sires had abnormalities in elevated plus maze and prepulse inhibition of startle, but normal spatial memory and impaired expression of hypothalamic, but not hippocampal, Kcc2. In contrast to exposed F0, their progeny exhibited normal corticosterone responses to stress. Bisulphite sequencing revealed increased CpG site methylation in the Kcc2 promoter in F0 sperm and F1 male hippocampus and hypothalamus that was in concordance with the changes in Kcc2 expression in specific F1 groups. CONCLUSIONS: Neonatal exposure to sevoflurane can affect the next generation of males through epigenetic modification of Kcc2 expression, while F1 females are at diminished risk.

[Injuries to blood vessels near the heart caused by central venous catheters]. / Verletzungen herznaher Gefäße durch zentralvenöse Katheter.

Injuries to blood vessels near the heart can quickly become life-threatening and include arterial injuries during central venous puncture, which can lead to hemorrhagic shock. We report 6 patients in whom injury to the subclavian artery and vein led to life-threatening complications. Central venous catheters are associated with a multitude of risks, such as venous thrombosis, air embolism, systemic or local infections, paresthesia, hemothorax, pneumothorax, and cervical hematoma, which are not always immediately discernible. The subclavian catheter is at a somewhat lower risk of catheter-associated sepsis and symptomatic venous thrombosis than approaches via the internal jugular and femoral veins. Indeed, access via the subclavian vein carries a substantial risk of pneumo- and hemothorax. Damage to the subclavian vein or artery can also occur during deliberate and inadvertent punctures and result in life-threatening complications. Therefore, careful consideration of the access route is required in relation to the patient and the clinical situation, to keep the incidence of complications as low as possible. For catheterization of the subclavian vein, puncture of the axillary vein in the infraclavicular fossa is a good alternative, because ultrasound imaging of the target vessel is easier than in the subclavian vein and the puncture can be performed much further from the lung.

Transfusion has no effect on recurrence in hepatitis C after liver transplantation.

BACKGROUND: The literature suggests that blood product transfusions have a negative impact on the survival of liver transplant patients. We investigated the impact of intraoperative blood product usage on the survival of liver transplantation patients being transplanted for hepatitis C-related end-stage liver disease. In addition, we analyzed a potentially more sensitive metric, namely disease recurrence and fibrosis progression, obtained from follow-up liver biopsies. METHODS: We retrospectively studied 194 consecutive patients with hepatitis C virus (HCV) undergoing liver transplantation. To investigate the effect of red blood cell (RBC) or platelet transfusions on post-transplant HCV recurrence, hepatic biopsy data from 4 months and 1 year after transplantation were studied. In addition, survival data were analyzed. RESULTS: There was no effect of intraoperative RBC or platelet transfusion on either 1- or 5-year patient survival following liver transplantation. There was no difference in HCV disease recurrence or progression of hepatic fibrosis at 4 months or 1 year attributable either to RBC or to platelet transfusion. CONCLUSION: This study was not able to confirm an effect on the survival of HCV-infected liver transplant patients related to intraoperative transfusion of RBCs or platelets. In addition, these transfusions had no effect on HCV recurrence or fibrosis progression. This is not to condone a liberal transfusion practice, but rather to reassure that when clinically indicated, transfusion does not have a significant impact on patient survival or disease recurrence in HCV-infected liver transplant patients.

Effects of elevating the head of bed on interface pressure in volunteers.

OBJECTIVE: Intensive care unit patients are at particular risk for pressure ulcers and ventilator-associated pneumonia. Current guidelines recommend that mechanically ventilated patients be kept in a semirecumbent position with the head of bed elevated 30 degrees -45 degrees to prevent aspiration and ventilator-associated pneumonia. We tested the effects of elevating the head of bed on the interface pressure between the skin of the sacral area and the bed with healthy volunteers. INTERVENTIONS: Interface pressure profiles of the sacral area were obtained for the 0 degrees , 10 degrees , 20 degrees , 30 degrees , 45 degrees , 60 degrees , and 75 degrees head of bed elevated positions from 15 subjects (14 men, one woman). MEASUREMENTS AND MAIN RESULTS: Peak sacral interface pressures increased with large increases in head of bed elevation. The 30 degrees , 45 degrees , 60 degrees , and 75 degrees head of bed positions all had peak interface pressures that were significantly (p < 0.02) greater than the supine measurement and also were different from all other head of bed positions. Affected areas, defined as areas over which an interface pressure >or=32 mm Hg was obtained, increased with large elevation of the head of bed. The affected areas of the 45 degrees , 60 degrees , and 75 degrees head of bed positions were significantly greater than the supine position and were also significantly different from all other head of bed positions. CONCLUSIONS: Raising the head of bed to 30 degrees or higher on a intensive care unit bed increases the peak interface pressure between the skin at the sacral area and support surface in healthy volunteers. At 45 degrees head of bed elevation or higher, the affected area attributed to a skin-intensive care unit bed interface pressure >or=32 mm Hg increased as well. Further study is needed to determine whether the increased peak interface pressures and affected areas that result from raising the head of bed actually increase the incidence of pressure ulcer formation.

An audible indication of exhalation increases delivered tidal volume during bag valve mask ventilation of a patient simulator.

Self-inflating manual resuscitators (SIMRs) can mislead caregivers because the bag, unlike a Mapleson-type device, reinflates even without patient exhalation. We added a whistle as an audible indicator to the exhalation port of a SIMR. In randomized order, each participant provided two sets of breaths via mask ventilation with a SIMR, one with and one without audible feedback, to a Human Patient Simulator modified to log lung volume changes. The last three breaths in each set were used to compare average tidal volume (Vt) under both conditions. Eighty-seven advanced cardiac life support trainees (54 males, 33 females) with clinical experience averaging 6.4 +/- 9.4 yr were recruited. Average Vt delivered with the standard SIMR was 486 +/- 166 mL and 624 +/- 96 mL with the modified SIMR. Average Vt delivered by a modified SIMR was significantly larger by 40% when it followed standard SIMR use and 19% when using the modified SIMR first. Use of a SIMR with an audible indicator of exhalation significantly (P < 0.001) increased mask ventilation of a patient simulator, suggesting that mask ventilation of a patient with a SIMR may also be increased by objective, real-time feedback of exhaled Vt.

Comparison of central corneal endothelial cell numbers with peripheral areas.

Using a specific fixation device on a group of patients, we compared corneal endothelial cell count areas above, below, and temporally with the central corneal cell counts. Although younger patients, the central cornea mirrored the peripheral cell counts; peripheral counts were similar in each group. Patients with intraocular lenses had fewer cells than patients with uneventful cataract extraction, and the central cornea was representative in the cataract group. Only in the intraocular lens group was there a small difference between central endothelial cell counts and the temporal and inferior cell counts; but even this difference was significantly less than that seen in patients with intracapsular cataract extraction.

Aspirin stabilization of the blood-aqueous barrier in the human eye.

After anterior chamber paracentesis, patients responded with an effusion of protein into the anterior chamber. Pretreatment with aspirin significantly decreased this trauma-induced, probably prostaglandin-mediated, disruption of the blood-aqueous barrier. Protein levels in aqueous humor of human eyes were measured in samples taken initially and five minutes after anterior chamber tap. The protein rise of 53% in five minutes in control patients was limited to 7% in patients pretreated with systemically administered aspirin. Prostaglandin mechanisms may be important in human ocular trauma and prostaglandin synthetase inhibitors may control the reaction to surgical trauma.

Effects of aortic occlusion on regional spinal cord blood flow and somatosensory evoked potentials in sheep.

Somatosensory evoked potentials (SEPs) were recorded continuously during aortic occlusion in sheep, with simultaneous measurement of spinal cord blood flow (SCBF) by radiolabeled microspheres. Aortic occlusion was associated with disappearance of the SEPs in seven of nine sheep in 7.8 +/- 4.1 (SD) minutes. SCBF at the time of initial cross clamping and 30 minutes after the onset of ischemia revealed a severe reduction in white and gray matter flow in the thoracolumbar cord. Release of the aortic clamp was associated with reactive hyperemia in these ischemic regions. In two animals, the SEP persisted during aortic cross clamping. The total SCBF in the thoracic and lumbar regions of these two animals exceeded 20 ml/100 g/min after 30 minutes of ischemia and was significantly greater than the flow recorded in sheep whose evoked response disappeared. The relation between spinal cord ischemia and evoked potential alterations is discussed in detail.

Effects of induced hypotension during experimental vasospasm: a neurological, electrophysiological, and pathological analysis.

Vasospasm of the vertebrobasilar system was induced in seven dogs by the intracisternal injection of autologous blood. Somatosensory and brain stem auditory evoked potentials were recorded before and after the induction of angiographically confirmed vasospasm. Additionally, somatosensory evoked potentials were monitored during graded hypotension to 40 mm Hg. There was no significant alteration in the evoked potentials by vasospasm or hypotension. Detailed clinical examination and postmortem histopathological studies did not demonstrate any focal neurological deficit or infarction attributable to vasospasm. Previous studies have noted close correlations between decreased cerebral blood flow and evoked potential alterations. Induced hypotension to a mean arterial pressure of 40 mm Hg in the presence of documented vasospasm was not sufficient to cause evoked potential changes, focal neurological deficit, or pathological evidence of infarction in the canine model.

Spinal anesthesia for nonpulmonary surgery in a lung transplant recipient.

The anesthetic implications for patients requiring anesthesia for surgery after lung transplantation have not been thoroughly studied. The use of spinal anesthesia in patients undergoing lumbar laminectomy has been well described. This case demonstrates the use of spinal anesthesia for lumbar laminectomy in a patient who had previously undergone a bilateral lung transplantation. Spinal anesthesia was used to minimize the risk of respiratory complications such as aspiration, atelectasis, and pneumonia that may be associated with administration of a general anesthetic.

Thoracic aortic occlusion: somatosensory evoked potential monitoring and neurologic outcome in a canine model.

Somatosensory evoked potentials (SEPs) were monitored in 17 canines during spinal cord ischemia induced by balloon occlusion of the thoracic aorta. Graded distal aortic hypotension to 40 mmHg in seven animals had no significant effect upon the evoked potential. A significant alteration in the SEP did result in 21 +/- 9.8 minutes when distal aortic pressures were reduced in a graded fashion below 30 mmHg. Acute occlusion of the thoracic aorta (10 animals, distal pressure 15-25 mmHg) was associated with a change in the SEP in 8.4 +/- 4.3 minutes. Continuation of aortic occlusion for 30 minutes beyond an evoked potential change resulted in a moderate to severe motor deficit in all cases. Somatosensory evoked potentials obtained 72-96 hours after the ischemic injury were closely correlated with sensory deficits, but were not predictive of motor examination. Histologic examination of the spinal cords demonstrated central gray necrosis of the lumbar region in all animals with a severe deficit, and a variable degree of neuronal loss in the intermediate and dorsal gray matter zones in animals with moderate deficits. This balloon occlusion method is relevant as a model of spinal cord injury during aortic occlusion, such as may occur during aortic surgery.

Low back pain following epidural blood patch.

A patient underwent outpatient knee arthroscopy with spinal anesthesia administered at the patient's request. The patient was discharged after a 3-hour recovery period. Three days later, the patient returned because of a headache that had begun the evening after surgery and progressively worsened. Treatment with caffeine and hydration for presumed postdural puncture headache resulted in relief for approximately 1 hour. An epidural blood patch was then performed and relieved symptoms for 3 hours until backache began and worsened over the next 7 hours. Computed axial tomography showed epidural air. After symptomatic treatment and observation overnight, the patient was released, and follow-up by telephone was planned. For 2 days, symptoms persisted. Therapy with aspirin 600 mg 4 times daily resulted in acute and significant relief. The backache resolved after 1 week. A review of the literature on backache following epidural blood patch is presented.

Endobronchial rupture from endotracheal reintubation with an endotracheal tube guide.

Endotracheal tube guides are often used to facilitate endotracheal tube exchange in patients whose airways are difficult to intubate. The absence of reported complications with this technique suggests it is a safe technique; however, we report a case of endobronchial rupture associated with such a guide. Diagnosis and management of tracheobronchial tears and alternative approaches to difficult reintubation are described.

High incidence of CO2 laser beam contact with the tracheal tube during operations on the upper airway.

Polyvinyl chloride tracheal tubes from 50 consecutive CO2 laser operations of the larynx and trachea were collected after tracheal extubation. In all cases, the helium protocol for laser operations was used, which includes the following: helium in the anesthetic gas mixture at 60% or more during laser resection (FIO2 less than or equal to 0.4); tracheal intubation with plain, unmarked polyvinyl chloride tubes; laser power density less than or equal to 1,992 W/cm2; and laser bursts of less than or equal to 10-second duration. No tracheal tube fires or airway burns occurred. The polyvinyl chloride tubes were examined for marks caused by the laser, and cuffed tubes were tested for cuff viability. Of the 50 tubes examined, 18 were noncuffed and 32 were cuffed. Although most contacts did not penetrate the tubes, 58% of the tubes showed evidence of contact with the laser as a brown mark on the tube or as a cuff leak. Cuffed tubes were more likely to incur laser contact (69%) than noncuffed tubes (39%), a significant difference (p = 0.04). Most of the cuffed tubes that came in contact with the laser sustained damage at the cuff (77%). It was concluded that the risk of tracheal tube contact with a laser beam is at least 1 in 2, that cuffed tubes are more likely to be hit with a laser beam than noncuffed tubes, and that cuffed tubes that are hit usually sustain damage to the cuff. Because no fires occurred in this series despite frequent laser contact with the tube, these data indicate that the helium protocol helps to prevent polyvinyl chloride tube fires.

Very limited air elimination capability of the level 1 fluid warmer.

STUDY OBJECTIVE: To determine the volume of air in 1000-ml crystalloid bags before and after connection to an infusion set; and to determine the volume of air that is not eliminated by the air eliminator in the Level 1 fluid warming device (Level 1 Technologies, Inc., Rockland, MA) when air boluses of different volumes enter into the fluid warming set. DESIGN: Prospective analysis and laboratory investigation. SETTING: Operating room (OR) and research laboratory of a university hospital. INTERVENTIONS: Air was aspirated from 200 collapsible, 1000-ml crystalloid bags: 100 before being connected to an infusion set and 100 after being connected to a patient in the OR. A roller pump from a cardiopulmonary bypass machine was connected to a Level 1 D-300 fluid administration set to maintain a continuous flow of normal saline through its air eliminator at a flow that approximated gravity or two thirds maximal flow, which is the rate achieved when fluid is pressurized to 300 mmHg throughout the system. Different volumes of air were administered and the air that passed through the air eliminator was measured. MEASUREMENTS AND MAIN RESULTS: Nonspiked bags contained 56.2 +/- 4 ml (mean +/- SD) of air (range 43-66 ml), and spiked bags contained 61.2 +/- 13 ml of air (range 4-102 ml), a significant difference (p < 0.0001). The amount of air passing through the air eliminator differed significantly at gravity and at two thirds maximal flow with boluses of 5, 10, 20, and 30 ml of air (p < 0.0001), but not with the 60 ml bolus of air. The amount of air passing through the eliminator also differed significantly (p < 0.0001) between boluses of different sizes at each flow rate. At the higher flow rate, even small boluses of air were not reliably eliminated; up to 56% of a 5 ml air bolus passed through the eliminator. CONCLUSION: Air must be rigorously eliminated from all fluid containers because of the limited air elimination capability of the Level 1 air eliminator.

Intraoperative pulse oximetry: frequency and distribution of discrepant data.

STUDY OBJECTIVE: To determine the types of discrepant data during intraoperative pulse oximetry and their frequency and duration. DESIGN: Prospective study. SETTING: University medical center. PATIENTS: 46 consecutive ASA physical status I-III patients undergoing general anesthesia for elective surgical operations. MEASUREMENTS AND MAIN RESULTS: With an integrated computer algorithm on the pulse oximeter and another computer linked to it, data were screened and the frequency and distribution of the following oximeter signals recorded: absent; low quality or interrupted, as detected by the pulse oximeter algorithm; nonphysiologic, identified by the personal computer as a heart rate change greater than 10 beats per minute within 2 consecutive 2-second samples, with no similar abrupt change reported simultaneously on ECG. The number of episodes per hour of discrepant oximeter data and the duration of the episodes were recorded by phase of anesthesia: induction, maintenance, and emergence. Discrepant data occurred most frequently and lasted longest during emergence (p < 0.05); the majority of episodes of discrepant data during emergence lasted less than 12 seconds. Excluding discrepant data that lasted less than 12 seconds decreased the frequency of discrepant data by 63% and excluding those that lasted less than 30 seconds decreased the frequency of discrepant data by 93%. CONCLUSIONS: Pulse oximeters frequently report discrepant data intraoperatively, most frequently during emergence from anesthesia. An alarm delay triggered by discrepant data and lasting 12 to 30 seconds would keep most discrepant data from becoming false alarms and, thus, may reduce distracting sound pollution in the operating room.

Duration of carbon dioxide absorption by soda lime at low rates of fresh gas flow.

STUDY OBJECTIVE: To determine the impact of a low fresh gas flow rate on the duration of carbon dioxide (CO2) absorption by soda lime. DESIGN: Nonclinical, experimental. SETTING: Experimental laboratory. METHODS: In vitro test with Sodasorb and a semiclosed breathing circle ventilating a test lung with a CO2 inflow of 250 ml per minute. Fresh gas flow rates of 0.25, 0.5, 1, 2, and 4 L/min were studied. MEASUREMENTS AND MAIN RESULTS: CO2 was measured at the breathing circuit test lung interface with a mainstream capnometer. Duration of CO2 absorption was determined as the time for the inspired CO2 tension (PICO2) to increase from 0 mm to 7 mm of mercury. The times of this interval were recorded four times for each fresh gas flow rate and compared by analysis of variance; p less than 0.05 was considered significant. Time to soda lime failure was significantly longer at 2 L/min than at 1 L/min fresh gas flow and at 1 L/min than at 0.25 L/min fresh gas flow. CONCLUSION: Because soda lime color indicators are unreliable, when a semiclosed breathing circle is used at a low rate of fresh gas flow without CO2 monitoring, the CO2 absorbent must be replaced more frequently.

In vitro comparison of central venous catheters for aspiration of venous air embolism: effect of catheter type, catheter tip position, and cardiac inclination.

STUDY OBJECTIVE: To test the relative efficiency of balloon-tipped and plain catheters for aspiration of venous air embolism. DESIGN: The following four single-lumen central venous catheters were studied in a silastic model of the right atrium, tricuspid valve, and vena cavae: (1) the 16-gauge single-orifice catheter; (2) the 14-gauge Bunegin-Albin multiorifice catheter; (3) the 7-Fr pulmonary angiography catheter with balloon distal to orifices; (4) the 7-Fr pulmonary angiography catheter with balloon proximal to orifices. A 10% glycerol-water solution was circulated at 3.7 to 4.0 L/min. Catheter tips were positioned at 1 cm increments from -3 to +3 cm around the superior vena cava-right atrial junction with cardiac inclinations of 65 degrees and 80 degrees. Air (10 ml) was infused over 30 seconds; aspiration from the test catheter began 5 seconds later at 40 ml/min for 75 seconds. The balloon catheters were evaluated with the balloons inflated and deflated. SETTING: Experimental laboratory of a university-affiliated hospital. MEASUREMENTS AND MAIN RESULTS: Amounts of air aspirated were compared by analysis of variance and Tukey's multiple comparison, p less than 0.05, for all combinations. The 16-gauge single-orifice catheter tested best at a 65 degrees cardiac inclination with 86% of the venous air embolism recovered, while the 14-gauge Bunegin-Albin multiorifice catheter tested best at an 80 degrees cardiac inclination with 62% of the venous air embolism recovered. Both catheters functioned most efficiently at or above the superior vena cava-right atrial junction. CONCLUSIONS: This study demonstrated that efficacy of air recovery depends on catheter type, catheter tip position, and cardiac inclination. No benefit was derived from positioning the catheter tip inside the atrium or from using balloon-tipped catheters.

Monitoring technologies in the neonatal intensive care unit: implications for the detection of necrotizing enterocolitis.

Necrotizing enterocolitis is the most common and fulminant gastrointestinal disease affecting neonates. Its pathogenesis is heterogeneous and not clearly understood. Early detection could prevent some of the devastating consequences of this disease, but currently there is no noninvasive method of reliable early-stage detection. Here, we review various noninvasive monitoring technologies that have already been employed or show promise for early detection. Each method may have an important role after its technical difficulties are resolved. These are discussed in detail as they relate to various aspects of the putative pathophysiology of this devastating disease.