Sympathetic Nervous System Does Not Mediate Reflex Pupillary Dilation during Desflurane Anesthesia

Background: Pupil size is determined by an interaction between the sympathetic and parasympathetic divisions of the autonomic nervous system. Noxious stimulation dilates the pupil in both unanesthetized and anesthetized humans. In the absence of anesthesia, dilation is primarily mediated by the sympathetic nervous system. In contrast, pupillary dilation in cats given barbiturate or cloralose anesthesia is mediated solely by inhibition of the midbrain parasympathetic nucleus. The mechanism by which noxious stimuli dilate pupils during anesthesia in humans remains unknown. Accordingly, the authors tested the hypothesis that the pupillary dilation in response to noxious stimulation during desflurane anesthesia is primarily a parasympathetic reflex.

Methods: In six volunteers, the alpha-1 adrenergic receptors of the iris musculature were blocked by unilateral administration of topical dapiprazole; six other volunteers were given unilateral topical tropicamide to block the muscarinic receptors in the iris. Desflurane anesthesia was subsequently induced in all volunteers. Sympathetic nervous system activation, with reflex dilation of the pupil, was produced by noxious electrical stimulation during 4% and 8% end-tidal desflurane, and by a rapid 4%-to-8% step-up in the desflurane concentration. Pupil diameter and the change in pupil size induced by a light stimulus (light reflex amplitude) were measured with infrared pupillometry.

Results: Dapiprazole drops produced a Horner's miosis, but pupils were equally small after induction of anesthesia. Pupillary dilation after noxious stimulation and desflurane step-up was identical in the unblocked and dapiprazole-blocked pupils. After tropicamide administration, the pupil was dilated and the light reflex was completely inhibited. Noxious stimulation nonetheless produced a slight additional dilation.     

Mechanism of Pupillary Reflex Dilation in Awake Volunteers and in Organ Donors

Background: The mechanism of reflex pupillary dilation was investigated in eight patients who were declared brain dead after rupture of intracranial vascular malformations and in eight awake volunteers. The authors hypothesized that the reflex was primarily a spinal sympathetic reflex that would be blocked by topical application of the [alpha]1-adrenergic blocking agent dapiprazole and that it would be present in organ donors with intact spinal reflexes and no history of hypoxia.

Methods: In volunteers, pupil size was measured with an infrared pupillometer while brief painful electric stimuli were delivered to the finger. Pain was assessed with a visual analog scale and adjusted with each volunteer to equal 3 on a visual analog scale of 0-10. Subjects were studied before and after topical application of the [alpha]1-adrenergic antagonist dapiprazole. In organ donors, the authors measured pupil size after high-intensity tetanic electric stimulation and in dapiprazole-blocked and -unblocked pupils after surgically induced nociception.

Results: In volunteers, the pupil dilated 0.43 +/- 0.23 mm after nociceptive stimuli. Dapiprazole eyedrops blocked this dilation, confirming that the reflex in awake humans is primarily a sympathetic reflex. Baseline diameters were 5.7 +/- 0.5 mm before dapiprazole and 4.1 +/- 0.9 mm after dapiprazole. In organ donors, a tetanic electric current failed to dilate the pupil, whereas the skin incision dilated the pupil 0.4 +/- 0.4 mm, but this dilation was not blocked by dapiprazole.     

Scaphoid Fracture Repair Does Not Significantly Diminish Short-Term Participation in the National Football League

Background

Fixation of scaphoid fractures is recommended in elite athletes to hasten healing and return-to-sport times. Complications such as nonunion negatively affect athletic performance.

Questions/Purposes

The purpose of this study was to examine the prevalence and impact of scaphoid repair on National Football League (NFL) participation during athletes’ first season in the NFL, while identifying significant predictors for development of carpal arthritis and scaphoid nonunion.

Methods

A total of 1311 football athletes invited to the NFL Scouting Combine from 2012 to 2015 were evaluated for history of scaphoid fracture repair. Athlete demographics, surgical history, and imaging and physical examination findings were recorded. Future NFL participation based on draft status, games played, and games started during athletes’ first season were gathered using publicly available databases.

Results

Nineteen (1.4%) athletes underwent 24 operations for scaphoid repair. Limitations in wrist range of motion or strength were present in 47.4% of athletes with a history of repair. Arthritic changes were present in 32% of wrists, while radiographic nonunion was present in two athletes following scaphoid fracture. Defensive backs were observed to have a higher incidence for arthritic changes following repair compared to other positions. No significant difference in prospective NFL participation was found in athletes with a history of scaphoid repair than in those without.

Conclusions

Athletes with a history of scaphoid repair are not at significant risk for diminished participation during their first season in the NFL.

     

Naloxone Does Not Reverse the Pain-Reducing Effect of Vibratory Stimulation

Fifteen patients suffering from chronic epicondylitis pain who obtained alleviation of pain with vibratory stimulation were studied to investigate the possible role of endogenous opioids in the mediation of pain alleviation of vibratory stimulation. The patients' subjective pain intensity was rated using a graphic rating scale. In five patients the changes in peripheral blood flow before, during and after vibratory stimulation were also studied. After 30 min of mechanical vibratory stimulation at 100 Hz, patients were given a double-blind intravenous injection of naloxone or saline (placebo). Twelve patients did not experience reversal of pain relief from naloxone (0.4 mg). Reversal of the pain alleviation induced by vibratory stimulation was seen in two patients after i.v. injections of naloxone and in one patient after i.v. injections of naloxone or saline. When an i.m. injection of naloxone 0.01 mg/kg was administered before and during vibratory stimulation, none of the patients experienced an antagonistic effect of the pain-reducing effect of vibratory stimulation. The results suggest that the pain relief obtained with vibratory stimulation at 100 Hz is not associated with release of endogenous opioids.     

Utility of Nociceptive Flexion Reflex Threshold, Bispectral Index, Composite Variability Index and Noxious Stimulation Response Index as measures for nociception during general anaesthesia

Movement and haemodynamic responses to noxious stimuli during general anaesthesia are regarded as signs of nociception. We compared the Nociceptive Flexion Reflex Threshold (NFRT), Bispectral Index (BIS), Composite Variability Index (CVI), Noxious Stimulation Response Index (NSRI) and the calculated propofol/remifentanil effect-compartment concentrations (Ce) as predictors for such responses in 50 female subjects at laryngeal mask airway insertion and skin incision. The following prediction probabilities (PK-values) were obtained at laryngeal mask airway insertion and skin incision, respectively. For movement responses: NFRT = 0.77 and 0.72; p = 0.0001 and 0.004, respectively; BIS = 0.41 and 0.56, p = 0.29 and 0.5, respectively; CVI = 0.48 and 0.57, p = 0.76 and 0.88, respectively; NSRI = 0.49 and 0.76, p = 0.92 and 0.0001, respectively; propofol-Ce = 0.35 and 0.66, p = 0.04 and 0.03, respectively; remifentanil-Ce = 0.68 and 0.72, p = 0.01 and 0.003, respectively. For heart rate responses: NFRT = 0.68 and 0.75, p = 0.04 and 0.01, respectively; BIS = 0.37 and 0.59, p = 0.15 and 0.41, respectively; CVI = 0.41 and 0.44, p = 0.39 and 0.37, respectively; NSRI = 0.48 and 0.53, p = 0.84 and 0.78, respectively; propofol-Ce = 0.42 and 0.56, p = 0.39 and 0.53, respectively; remifentanil-Ce = 0.58 and 0.54, p = 0.35 and 0.73, respectively. We conclude that the NFRT best predicts movement and heart rate responses to noxious stimuli. Effect-compartment concentrations and NSRI also predict movement (but not heart rate) responses satisfactorily.     

Multilevel Surgery Improves Gait in Spastic Hemiplegia But Does Not Resolve Hip Dysplasia

Background  

Multilevel orthopaedic surgery may improve gait in Type IV hemiplegia, but it is not known if proximal femoral osteotomy combined with adductor release as part of multilevel surgery in patients with hip dysplasia improves hip development.     

Effects of Alfentanil on the Ventilatory Response to Sustained Hypoxia

Background: The ventilatory response to acute hypoxia is biphasic, with an initial rapid increase followed by a slower decline. In humans, there is evidence that the magnitude of the decline in ventilation is proportional to the size of the initial increase. This study was done to define the role of exogenous opioids in the ventilatory decline seen with prolonged hypoxia.

Methods: Ten healthy persons were exposed to isocapnic hypoxia for 25 min, followed by 5 min of isocapnic normoxia and 5 min of isocapnic hypoxia. These conditions were repeated during a computer-controlled alfentanil infusion.

Results: Serum alfentanil levels were constant among the volunteers (38 +/- 12 ng/ml). Alfentanil decreased both the initial and second acute hypoxic responses (from 1.27 +/- 0.73 to 0.99 +/- 0.39 l [middle dot] min-1 [middle dot] %-1, P < 0.05; and from 0.99 +/- 0.70 to 0.41 +/- 0.29 l [middle dot] min-1 [middle dot] %-1, P < 0.05, respectively). The magnitude of the decrease in ventilation during the 25 min of hypoxia was not changed (10 +/- 3.3 l/min for control; 12.3 +/- 7.5 l/min for alfentanil).     

Complete Response to Neoadjuvant Chemoradiation for Rectal Cancer Does Not Influence Survival

Background: Up to 30% of patients with locally advanced rectal cancer have a complete clinical or pathologic response to neoadjuvant chemoradiation. This study analyzes complete clinical and pathologic responders among a large group of rectal cancer patients treated with neoadjuvant chemoradiation.Methods: From 1987 to 2000, 141 consecutive patients with biopsy-proven, locally advanced rectal cancer were treated with preoperative 5-fluorouracil-based chemotherapy and radiation. Clinical restaging after treatment consisted of proctoscopic examination and often computed tomography scan. One hundred forty patients then underwent operative resection, with results tracked in a database. Standard statistical methods were used to examine the outcomes of those patients with complete clinical or pathologic responses.Results: No demographic differences were detected between either clinical complete and clinical partial responders or pathologic complete and pathologic partial responders. The positive predictive value of clinical restaging was 60%, and accuracy was 82%. By use of the Kaplan-Meier life table analysis, clinical complete responders had no advantage in local recurrence, disease-free survival, or overall survival rates when compared with clinical partial responders. Pathologic complete responders also had no recurrence or survival advantage when compared with pathologic partial responders. Of the 34 pathologic T0 tumors, 4 (13%) had lymph node metastases.Conclusions: Clinical assessment of complete response to neoadjuvant chemoradiation is unreliable. Micrometastatic disease persists in a proportion of patients despite pathologic complete response. Observation or local excision for patients thought to be complete responders should be undertaken with caution.Presented in part at the 54th Annual Cancer Symposium of the Society of Surgical Oncology, Washington, DC, March 15–18, 2001.     

Aprotinin Does Not Diminish Blood Loss in Elective Operations for Infrarenal Abdominal Aneurysms: A Randomized Double-Blind Controlled Trial

Surgery for abdominal aneurysm is associated with substantial blood loss. In cardiac surgery, aprotinin, a fibrinolysis inhibitor, has shown to reduce blood loss significantly. Our aim was to assess the effect of aprotinin, when administered during elective surgery of infrarenal abdominal aneurysm, on coagulation, blood loss, and morbidity. A double-blind randomized trial was performed on 35 consecutive patients. They were randomized to either an aprotinin or a placebo group. The aprotinin group received 2,000,000 kallikrein inhibiting units (KIU) of aprotinin (500,000 KIU in 50 mL NaCl 0.9%) as a starting dose, followed by 500,000 KIU per hour during the operation. The placebo group received equal amounts of only NaCl 0.9%. During the operation and 24 hr thereafter, blood samples were taken to assess coagulation factors. Blood loss was measured in suction devices and swabs. All patients were followed until their discharge from the hospital. Statistical analysis was performed by independent t-test or Mann-Whitney U-test and chi-squared test. There was no significant difference in the amount of blood loss or the amount of blood products administered between the two groups. Morbidity and mortality were also comparable. In both groups, consumption of clotting factors could be detected, indicating activation of the coagulation cascade. However, in the aprotinin group, the α₂-antiplasmin level was raised during surgery, indicating inhibition of fibrinolysis. Administration of aprotinin during elective operations for infrarenal aortic aneurysm induces inhibition of fibrinolysis. However, it does not significantly reduce blood loss or the need for blood products.This paper was presented as an oral presentation at the Seventeenth Meeting of the European Society for Vascular Surgery, Dublin, Ireland, September 5-7, 2003.     

Xenon Does Not Impair the Responsiveness of Cardiac Muscle Bundles to Positive Inotropic and Chronotropic Stimulation

Background: Most volatile anesthetics exhibit a direct myocardial depressant effect. This side effect often limits their applicability in patients with impaired cardiac function. Xenon is a new gaseous anesthetic that did not show any adverse cardiovascular effects in clinical and experimental studies. The authors tested the hypothesis that xenon does not affect myocardial contractility or the positive inotropic effect of isoproterenol, calcium, and increase in pacing rate in isolated guinea pig ventricular muscle bundles.

Methods: Thin ventricular muscle bundles from guinea pig hearts with a mean diameter of 0.4-0.45 mm were prepared under stereomicroscopic control. Force of contraction and contraction times were studied in muscles superfused with medium equilibrated with either 65% xenon and 35% oxygen (xenon group), 1.2% isoflurane in oxygen (isoflurane group), or 65% nitrogen and 35% oxygen (control group). In addition, the positive inotropic effects of calcium, isoproterenol (10-10 - 3 x 10-8 m) and increasing frequency (0.5-2 Hz) were studied during xenon and isoflurane exposure.

Results: In contrast to isoflurane, xenon did not alter myocardial force of contraction or contraction times. The positive inotropic effect of isoproterenol, calcium, and increasing pacing frequencies did not differ between the muscles exposed to xenon and the control group. Isoflurane elicited the expected negative inotropic effect (30% reduction of force of contraction) but did not impair the response to inotropic stimuli.     

Isoflurane Blunts Electroencephalographic and Thalamic-Reticular Formation Responses to Noxious Stimulation in Goats

Background: Anesthetics, including isoflurane, depress the electroencephalogram (EEG). Little is known about the quantitative effects of isoflurane on EEG and subcortical electrical activity responses to noxious stimulation. The authors hypothesized that isoflurane would depress the results of EEG and subcortical response to noxious stimulation at concentrations less than those needed to suppress movement. Furthermore, determination of regional differences might aid in elucidation of sites of anesthetic action.

Methods: Ten goats were anesthetized with isoflurane, and minimum alveolar concentration (MAC) was determined using a noxious mechanical stimulus. Depth electrodes were inserted into the midbrain reticular formation and thalamus. Needle electrodes placed in the skull periosteum measured bifrontal and bihemispheric EEG. The noxious stimulus was applied at each of four anesthetic concentrations: 0.6, 0.9, 1.1, and 1.4 MAC.

Results: At an isoflurane concentration of 0.6 MAC, the noxious stimulus activated the midbrain reticular formation, thalamic, and bifrontal-hemispheric regions, as shown by decreased high-amplitude, low-frequency power. For all channels combined (mean +/- SD), total (-33 +/- 7%), delta (-47 +/- 12%), theta (-23 +/- 12%), and alpha (-21 +/- 6%) power decreased after the noxious stimulus (P< 0.001); beta power was unchanged. At 0.9 MAC, total (-35 +/- 5%), delta (-42 +/- 7%), theta (-35 +/- 8%), and alpha (-23 +/- 11%) power decreased after the noxious stimulus (P< 0.001); beta power was unchanged. At 1.1 MAC only one site, and at 1.4 MAC, no site, had decreased power after the noxious stimulus.     

Experimental Comparison of Monofile Light and Heavy Polypropylene Meshes: Less Weight Does Not Mean Less Biological Response

Background Mesh implantation is a standard procedure in hernia repair. It provides low recurrence rate but increases complication rate due to foreign-body reaction induced by alloplastic materials in surrounding tissues. It is believed that biocompatibility of meshes may be improved by reducing their weight per meter squared (m²) and altering the implant structure. Aim The aim of this study was to evaluate the effect of weight and structure as determinants of mesh biocompatibility. Method Thirty-six Wistar rats were studied. In 12 animals, conventional polypropylene (heavy) meshes (HM) were implanted; in other 12, material-reduced (light) microporous polypropylene meshes (LM); and the remaining 12 served as a sham-operated control group. Meshes were explanted after 21 and 90 days (6 animals per group). All samples were examined by light and electron microscopies. Integration of meshes in surrounding tissue, inflammatory response, fibrotic reactions, and structural changes were recorded. Quantification of the inflammatory response was achieved by CD-68 marking of macrophages and counting their number per surface unit. Results After 21 days, there was no significant difference in thickness of surrounding connective tissue between meshes in all groups studied. After 90 days, thickness of connective tissue decreased in both groups, and fibrotic reaction in the mesh bed was significantly less in the HM group. Total amount of macrophages per millimeter squared (mm²) decreased with time in HM and LM samples but was significantly lower in the HM group on day 21 (43.5%) and day 90 (46.7%). Conclusion This study found worse biocompatibility of LM compared with HM. Thus, the amount of implanted mesh was not the main determinant of biocompatibility (expressed as successful incorporation and diminished foreign-body reaction) but the size of the pores.     

Isoflurane and Sevoflurane Augment Norepinephrine Responses to Surgical Noxious Stimulation in Humans

Background: Suppression of hypertensive response to noxious stimulation by volatile anesthetics may be a result of suppression of the stimulation-induced norepinephrine response or that of the cardiovascular response to catecholamines, or both. The suppression of the cardiovascular response is established, but that of norepinephrine response has not been confirmed. The authors hypothesized that the suppression of cardiovascular response but not that of norepinephrine response plays a major role in suppressing the noxious stimulation-induced hypertensive response by volatile anesthetics.

Methods: Forty healthy donors for living-related liver transplantation were allocated to four groups: receiving 1.2% (end-tidal) isoflurane in oxygen and nitrogen, 2.0% isoflurane, 1.7% sevoflurane, or 2.8% sevoflurane. The intraoperative plasma norepinephrine and epinephrine concentrations, arterial blood pressure and pulse rate were measured for the first 15 min of surgery and were compared with the preoperative values.

Results: Norepinephrine and epinephrine concentrations both increased intraoperatively in all four groups. The values of maximum increase the area under the concentration-versus-time curve of norepinephrine were greater in the high dose groups of both anesthetics. The intraoperative blood pressure did not differ by different doses of anesthetics, and the degree of increase of blood pressure was not proportional to the plasma catecholamine concentrations.     

Monitoring of Immobility to Noxious Stimulation during Sevoflurane Anesthesia Using the Spinal H-reflex

Background: The spinal H-reflex has been shown to correlate with surgical immobility, i.e., the absence of motor responses to noxious stimulation, during isoflurane anesthesia. Here, the authors established individual concentration-response functions for H-reflex amplitude and tested the predictive power of the H-reflex for movement responses during sevoflurane anesthesia in comparison to electroencephalographic parameters. In addition, they investigated the effect of noxious stimulation on the H-reflex itself.

Methods: The authors studied 12 female patients during sevoflurane anesthesia before surgery. The sevoflurane concentration was increased, a laryngeal mask was inserted, and then the sevoflurane concentration was decreased until H-reflex amplitude (recorded over the soleus muscle) recovered. Thereafter, the end-tidal sevoflurane concentration was kept at a constant value close to the minimum alveolar concentration for suppression of movement responses after tetanic stimulation (MACtetanus), determined by the Dixon up-down method. Pharmacodynamic modeling of H-reflex amplitude and of the Bispectral Index was performed, and predictive values for motor responses to noxious electrical stimulation (50 Hz, 60 mA tetanus, volar forearm) were compared using the prediction probability.

Results: Concentration-dependent depression of H-reflex amplitude by sevoflurane was well modeled (median r2 = 0.97) by a sigmoid function with a median EC50 of 1.5 vol% and a median slope parameter of 3.7, much steeper than the slope for the Bispectral Index. MACtetanus calculated by logistic regression was 1.6 vol%. H-reflex amplitude predicted motor responses to noxious stimulation with a prediction probability of 0.76, whereas the prediction probability for Bispectral Index and spectral edge frequency (SEF95) were not different from chance alone. Noxious stimulation was followed by a substantial increase of H-reflex amplitude for several minutes, whereas the Bispectral Index and SEF95 exhibited no significant changes.     

Pain Relief in Complex Regional Pain Syndrome due to Spinal Cord Stimulation Does Not Depend on Vasodilation

Background: Spinal cord stimulation (SCS) is known to relieve pain in patients with complex regional pain syndrome (CRPS) and, in general, to cause vasodilation. The vasodilatory effect of SCS is hypothesized to be secondary to inhibition of sympathetically mediated vasoconstriction, or through antidromic impulses resulting in release of vasoactive substances. The aim of the present study was to assess whether pain relief in CRPS after SCS is, in fact, dependent on vasodilation. In addition, we tried to determine which of the potential mechanisms may cause the vasodilatory effect that is generally found after SCS.

Methods: Twenty-four of 36 patients with unilateral CRPS responded to the test of SCS. Twenty-two of these 24 responders (hand, n = 14; foot, n = 8) who had undergone previous sympathectomy were enrolled for the study. In addition, 20 control subjects (10 controls for each extremity) were studied. By means of laser Doppler flowmetry, the skin microcirculation of the patients was measured bilaterally while the SCS system was switched off and while it was activated. Control subjects (n = 20) were tested once only. The ratio of the rest flow at heart level and the dependent position was defined as the vasoconstriction index.

Results: Both in affected hands and feet, patients were found to have lower vasoconstriction indices (P < 0.01) as compared with controls, indicating a decreased sympathetic tone. Applying SCS did not result in any microcirculatory change as compared with baseline or the contralateral clinically unaffected side.