Estimating pulsatile ocular blood volume from intraocular pressure, ocular pulse amplitude, and axial length.

The purpose of this study was to develop a method of estimating pulsatile ocular blood volume (POBV) from measurements taken during an ophthalmic exam, including axial length and using a tonometer capable of measuring intraocular pressure (IOP) and ocular pulse amplitude (OPA). Unpublished OPA data from a previous invasive study was used in the derivation, along with central corneal thickness (CCT) and axial length (AL), as well as IOP from the PASCAL dynamic contour tonometer (DCT) and intracameral (ICM) measurements of IOP for 60 cataract patients. Intracameral mean pressure was set to 15, 20, and 35 mmHg (randomized sequence) in the supine position, using a fluid-filled manometer. IOP and OPA measurements were acquired at each manometric setpoint (DCT and ICM simultaneously). In the current study, ocular rigidity (OR) was estimated using a published significant relationship of OR to the natural log of AL in which OR was invasively measured through fluid injection. Friedenwald's original pressure volume relationship was then used to derive the estimated POBV, delivered to the choroid with each heartbeat as a function of OR, systolic IOP (IOPsys), diastolic IOP (IOPdia), and OPA, according to the derived equation POBV = log (IOPsys/IOPdia) / OR. Linear regression analyses were performed comparing OPA to OR and calculated POBV at each of the three manometric setpoints. POBV was also compared to OPA/IOPdia with all data points combined. Significance threshold was p < 0.05. OR estimated from AL showed a significant positive relationship to OPA for both DCT (p < 0.011) and ICM (p < 0.006) at all three manometric pressure setpoints, with a greater slope for lower IOP. Calculated POBV also showed a significant positive relationship to OPA (p < 0.001) at all three setpoints with greater slope at lower IOP, and a significant negative relationship with IOPdia. In the combined analysis, POBV showed a significant positive relationship to OPA/ IOPdia (p < 0.001) in both ICM and DCT measurements with R2 = 0.9685, and R2 = 0.9589, respectively. POBV provides a straight-forward, clinically applicable method to estimate ocular blood supply noninvasively. Higher IOP in combination with lower OPA results in the lowest values of POBV. The simplified ratio, OPA/ IOPdia, may also provide a useful clinical tool for evaluating changes in ocular blood supply in diseases with a vascular component, such as diabetic retinopathy and normal tension glaucoma. Future studies are warranted.

Comparative analgesic efficacy and safety of intermittent local anaesthetic epidural bolus for labour: a systematic review and meta-analysis.

BACKGROUND: Continuous epidural infusion (CEI) is commonly used for labour analgesia, but concerns over potential motor block, second-stage labour complications, and ineffective analgesia in late labour have prompted examining intermittent epidural bolus (IEB) as an alternative. However, evidence comparing these modalities is conflicting. The meta-analysis evaluates the analgesic efficacy of CEI vs IEB. METHODS: Databases were searched for trials comparing CEI to IEB for labour analgesia. The two co-primary outcomes were risk of breakthrough pain and difference in area under the curve (AUC) for pain scores during the first 4 h post-epidural initiation. Local anaesthetic consumption, maternal outcomes (i.e. delivery mode, labour duration, and maternal satisfaction), and side-effects of epidural analgesia were also evaluated. Results were pooled using random-effects modelling. Trial sequential analysis (TSA) was used to evaluate evidence reliability. RESULTS: Twenty-seven studies (3133 patients) were analysed. Compared with CEI, IEB decreased risk of breakthrough pain by 38% (risk ratio [95% confidence interval {CI}] of 0.62 [0.48, 0.81]; P=0.0004; I2=47%; 1164 patients) and reduced AUC of pain during the 4 h interval by 32.9% (mean difference [95% CI] of -16.7 mm h-1 [-18.9, -14.4]; P<0.0001; 1638 patients). Intermittent epidural bolus enhanced maternal satisfaction, shortened labour duration, decreased motor block, and reduced local anaesthetic consumption. The difference between the two groups was not statistically significant for epidural side-effects or mode of delivery. The TSA indicated adequate power for reliable inferences. CONCLUSIONS: Intermittent epidural bolus provides improved labour pain control during the first 4 h after epidural initiation with less breakthrough pain. Moderate- to high-quality evidence of intermittent epidural bolus superiority support its use as a safe and effective continuous epidural infusion alternative for labour analgesia.

Continuous Epidural Hydromorphone Infusion for Post-Cesarean Delivery Analgesia in a Patient on Methadone Maintenance Therapy: A Case Report.

The prevalence of opioid use disorder (OUD) in the United States has more than quadrupled over the past two decades. This patient population presents a number of challenges to clinicians, including difficult pain management after surgical procedures due to the development of opioid tolerance. Significantly greater opioid consumption and pain scores after cesarean delivery have been reported in patients with OUD compared to other obstetric patients. A multi-modal analgesic regimen is generally recommended, but there are few well-established pain management strategies after cesarean delivery specific to patients with OUD. We present the case of a patient with OUD maintained on daily methadone that received a continuous epidural hydromorphone infusion for post-cesarean analgesia, a technique not previously reported in obstetric patients and only rarely described for patients undergoing other surgical procedures. The patient received epidural anesthesia for cesarean delivery, and after surgery, the epidural catheter was left in place for the epidural hydromorphone infusion, initiated at 140 mcg/hr and continued for approximately 40 hrs. This strategy reduced her average daily oral opioid consumption by 97%, reduced self-reported pain scores, shortened the length of hospitalization and improved ability to ambulate compared to her previous cesarean delivery. The use of continuous epidural hydromorphone infusion was effective in this case, and this analgesic technique may also be applicable to other types of surgical procedures with the potential for significant post-operative pain, particularly in patients with OUD.

Characteristics of the cerebrospinal fluid pressure waveform and craniospinal compliance in idiopathic intracranial hypertension subjects.

BACKGROUND: Idiopathic intracranial hypertension (IIH) is a condition of abnormally high intracranial pressure with an unknown etiology. The objective of this study is to characterize craniospinal compliance and measure the cerebrospinal fluid (CSF) pressure waveform as CSF is passively drained during a diagnostic and therapeutic lumbar puncture (LP) in IIH. METHODS: Eighteen subjects who met the Modified Dandy Criteria, including papilledema and visual field loss, received an ultrasound guided LP where CSF pressure (CSFP) was recorded at each increment of CSF removal. Joinpoint regression models were used to calculate compliance from CSF pressure and the corresponding volume removed at each increment for each subject. Twelve subjects had their CSFP waveform recorded with an electronic transducer. Body mass index, mean CSFP, and cerebral perfusion pressure (CPP) were also calculated. T-tests were used to compare measurements, and correlations were performed between parameters. RESULTS: Cerebrospinal fluid pressure, CSFP pulse amplitude (CPA), and CPP were found to be significantly different (p < 0.05) before and after the LP. CSFP and CPA decreased after the LP, while CPP increased. The craniospinal compliance significantly increased (p < 0.05) post-LP. CPA and CSFP were significantly positively correlated. CONCLUSIONS: Both low craniospinal compliance (at high CSFP) and high craniospinal compliance (at low CSFP) regions were determined. The CSFP waveform morphology in IIH was characterized and CPA was found to be positively correlated to the magnitude of CSFP. Future studies will investigate how craniospinal compliance may correlate to symptoms and/or response to therapy in IIH subjects.

From Bad to Worse: Paraganglioma Diagnosis during Induction of Labor for Coexisting Preeclampsia.

Pheochromocytomas and extra-adrenal paragangliomas are catecholamine-secreting tumors that rarely occur in pregnancy. The diagnosis of these tumors in pregnancy can be challenging given that many of the signs and symptoms are commonly attributed to preeclampsia or other more common diagnoses. Early diagnosis and appropriate management are essential in optimizing maternal and fetal outcomes. We report a rare case of a catecholamine-secreting tumor in which diagnosis occurring at the time labor was being induced for concomitant preeclampsia with severe features. Her initial presentation in hypertensive crisis with other symptoms led to diagnostic workup for secondary causes of hypertension and led to eventual diagnosis of paraganglioma. Obtaining this diagnosis prior to delivery was essential, as this led to prompt multidisciplinary care, changed the course of her clinical management, and ultimately enabled good maternal and fetal outcomes. This case highlights the importance of maintaining a high index of suspicion for secondary causes of hypertension and in obstetric patients and providing timely multidisciplinary care.

A Rare Case of C2 Sensory Blockade with Preserved Phrenic Nerve Function in an Obstetric Patient.

High neuraxial blockade is a serious complication in obstetric patients and requires prompt recognition and management in order to optimize patient outcomes. In cases of high neuroblockade, patients may present with significant hypotension, dyspnea, agitation, difficulty speaking or inability to speak, or even loss of consciousness. We report the unusual presentation of an obstetric patient that remained hemodynamically stable and had the preserved ability to initiate breaths despite sensory blockade up to C2. The presence of differential motor and sensory block documented in this case helped enable the patient to be managed with noninvasive ventilatory support until the high blockade regressed and we are not aware of any other similar reports in literature.

Ocular pressure waveform reflects ventricular bigeminy and aortic insufficiency.

Ocular pulse amplitude (OPA) is defined as the difference between maximum and minimum intraocular pressure (IOP) during a cardiac cycle. Average values of OPA range from 1 to 4 mmHg. The purpose of this investigation is to determine the source of an irregular IOP waveform with elevated OPA in a 48-year-old male. Ocular pressure waveforms had an unusual shape consistent with early ventricular contraction. With a normal IOP, OPA was 9 mmHg, which is extraordinarily high. The subject was examined by a cardiologist and was determined to be in ventricular bigeminy. In addition, he had bounding carotid pulses and echocardiogram confirmed aortic insufficiency. After replacement of the aortic valve, the bigeminy resolved and the ocular pulse waveform became regular in appearance with an OPA of 1.6-2.0 mmHg. The ocular pressure waveform is a direct reflection of hemodynamics. Evaluating this waveform may provide an additional opportunity for screening subjects for cardiovascular anomalies and arrhythmias.

A comparison of functional magnetic resonance imaging findings in children with and without a history of early exposure to general anesthesia.

BACKGROUND: Functional magnetic resonance imaging (fMRI) has been used to evaluate the long-term consequences of early exposure to neurotoxic agents. fMRI shows that different patterns of brain activation occur in ethanol-exposed subjects performing a go/no-go response inhibition task. Pharmacologically, ethanol and general anesthetics have similar receptor-level activity in the brain. This study utilizes fMRI to examine brain activation patterns in children exposed to general anesthesia and surgery during early brain development. METHODS: After obtaining Nationwide Children's Hospital IRB approval, a surgical database was utilized to identify children aged 10-17 years with a history of at least 1 h of exposure to general anesthetics and surgery when they were between 0 and 24 months of age. Age- and gender-matched children without anesthesia exposure were recruited as a control group. All subjects were scanned while being presented with a go/no-go response inhibition task. Reaction time and accuracy data were acquired, and the blood-oxygen-level-dependent (BOLD) fMRI signal was measured as a biomarker for regional neuronal activity. RESULTS: There were no differences in terms of performance accuracy and response time. The analysis did not reveal any significant activation differences in the primary region of interest (prefrontal cortex and caudate nucleus); however, activation differences were seen in other structures, including the cerebellum, cingulate gyrus, and paracentral lobule. CONCLUSIONS: Early anesthetic exposure and surgery did not affect accuracy, response time, or activation patterns in the primary region of interest during performance of the task. Intergroup differences in activation patterns in other areas of the brain were observed, and the significance of these findings is unknown. fMRI appears to be a useful tool in evaluating the long-term effects of early exposure to general anesthesia.

The comparative effects of lipid, epinephrine, and their combination in the reversal of bupivacaine-induced asystole in the isolated rat heart.

BACKGROUND: It remains unclear whether lipid combined with epinephrine is superior or inferior to either drug alone in treating bupivacaine cardiotoxicity. We compared the effects of lipid, epinephrine, and the combination of the two in reversing bupivacaine-induced asystole in the isolated rat heart model. We also measured the effects of lipid, epinephrine, and the combination of the two on bupivacaine content in cardiac tissue. METHODS: Hearts from male Sprague-Dawley rats were excised and retrograde-perfused in a nonrecirculating Langendorff preparation. Bupivacaine 100 µmol/L was perfused until 3 minutes after asystole. Two percent lipid and 30 µmol/L bupivacaine mixture was then perfused in the lipid group; 0.15 µg/mL epinephrine and 30 µmol/L bupivacaine mixture in the epinephrine group; 2% lipid combined with 0.15 µg/mL epinephrine and 30 µmol/L bupivacaine in the combination group; and 30 µmol/L bupivacaine alone in the control group. Recovery of heartbeat was defined as unassisted regular rhythm with a rate-pressure product (RPP) >10% of baseline for >1 minute. We compared the time from the end of 100 µmol/L bupivacaine infusion to recovery of heartbeat (T(recovery)) for each group. The variables of cardiac function were recorded for 40 minutes after recovery of heartbeat. The cardiac apex of each heart was taken for measurement of the bupivacaine content by liquid chromatography-tandem mass spectrometry at the end of the experiment. RESULTS: Time to recovery (T(recovery)) in the lipid and combination groups was significantly shorter than that in the epinephrine and control groups (P < 0.001), and T(recovery) in the epinephrine group was shorter than that in the control group (P < 0.05). The rank order of the mean RPP during the 40 minutes after recovery of heartbeat from highest to lowest was the combination group > the lipid and epinephrine groups > the control group (P < 0.01). The rank order of the highest RPP value during recovery (RPP(maximum)) and the ratio of RPP(maximum) to baseline value (RPP(maximum)/RPP(baseline)) from highest to lowest was the combination group > the lipid and epinephrine groups > the control group (P < 0.01). There was no significant difference between the lipid and epinephrine groups for RPP, RPP(maximum), and RPP(maximum)/RPP(baseline). Cardiac tissue bupivacaine content in the epinephrine and control groups was higher than that in the lipid and combination groups (P < 0.001). CONCLUSIONS: Lipid combined with epinephrine resulted in better recovery of cardiac function than either drug alone in reversal of bupivacaine-induced asystole in the isolated rat heart model.

Comparison between end-tidal CO2 and respiration volume per time for detecting BOLD signal fluctuations during paced hyperventilation.

Respiratory motion and capnometry monitoring were performed during blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) of the brain while a series of paced hyperventilation tasks were performed that caused significant hypocapnia. Respiration volume per time (RVT) and end-tidal carbon dioxide (ETCO(2)) were determined and compared for their ability to explain BOLD contrast changes in the data. A 35% decrease in ETCO(2) was observed along with corresponding changes in RVT. A best-fit ETCO(2) response function, with an average initial peak delay time of 12 s, was empirically determined. ETCO(2) data convolved with this response function was more strongly and prevalently correlated to BOLD signal changes than RVT data convolved with the corresponding respiration response function. The results suggest that ETCO(2) better models BOLD signal fluctuations in fMRI experiments with significant transient hypocapnia. This is due to hysteresis in the ETCO(2) response when moving from hypocapnia to normocapnia, compared to moving from normocapnia to hypocapnia.

The impact of physiologic noise correction applied to functional MRI of pain at 1.5 and 3.0 T.

This study quantified the impact of the well-known physiologic noise correction algorithm RETROICOR applied to a pain functional magnetic resonance imaging (FMRI) experiment at two field strengths: 1.5 and 3.0 T. In the 1.5-T acquisition, there was an 8.2% decrease in time course variance (σ) and a 227% improvement in average model fit (increase in mean R(2)(a)). In the 3.0-T acquisition, significantly greater improvements were seen: a 10.4% decrease in σ and a 240% increase in mean R(2)(a). End-tidal carbon dioxide data were also collected during scanning and used to account for low-frequency changes in cerebral blood flow; however, the impact of this correction was trivial compared to applying RETROICOR. Comparison between two implementations of RETROICOR demonstrated that oversampled physiologic data can be applied by either downsampling or modification of the timing in the RETROICOR algorithm, with equivalent results. Furthermore, there was no significant effect from manually aligning the physiologic data with corresponding image slices from an interleaved acquisition, indicating that RETROICOR accounts for timing differences between physiologic changes and MR signal changes. These findings suggest that RETROICOR correction, as it is commonly implemented, should be included as part of the data analysis for pain FMRI studies performed at 1.5 and 3.0 T.

Evaluation of a contact lens-embedded sensor for intraocular pressure measurement.

PURPOSE: To evaluate a novel contact lens-embedded pressure sensor for continuous measurement of intraocular pressure (IOP). METHODS: Repeated measurements of IOP and ocular pulse amplitude (OPA) were recorded in 12 eyes of 12 subjects in sitting and supine positions using 3 configurations of the dynamic contour tonometer: slit-lamp mounted (DCT), hand-held (HH), and contact lens-embedded sensor (CL). The IOP and OPA for each condition were compared using repeated measures ANOVA and the 95% limits of agreement were calculated. RESULTS: The sitting IOP (mean and 95% CI) for each configuration was DCT: 16.3 mm Hg (15.6 to 17.1 mm Hg), HH: 16.6 mm Hg (15.6 to 17.6 mm Hg), and CL: 15.7 mm Hg (15 to 16.3 mm Hg). The sitting OPA for each configuration was DCT: 2.4 mm Hg (2.1 to 2.6 mm Hg), HH: 2.4 mm Hg (2.1 to 2.7 mm Hg), and CL: 2.1 mm Hg (1.8 to 2.3 mm Hg). Supine IOP and OPA measurements with the CL and HH sensors were both greater than their corresponding sitting measurements, but were significantly less with the CL sensor than the HH sensor. The mean difference and 95% Limits of Agreement were smallest for the DCT and CL sensor comparisons (0.7+/-3.9 mm Hg) and widest for the CL and HH sensors (-1.9+/-7.25 mm Hg); these wider limits were attributed to greater HH measurement variability. CONCLUSIONS: The CL sensor was comparable to HH and DCT sensors with sitting subjects and is a viable method for measuring IOP and OPA. Supine measurements of IOP and OPA were greater than sitting conditions and were comparatively lower with the CL sensor. HH measurements were more variable than CL measurements and this influenced the Limits of Agreement for both sitting and supine conditions.

Functional magnetic resonance imaging studies of pain: an investigation of signal decay during and across sessions.

BACKGROUND: Several investigations into brain activation caused by pain have suggested that the multiple painful stimulations used in typical block designs may cause attenuation over time of the signal within activated areas. The effect this may have on pain investigations using multiple tasks has not been investigated. The signal decay across a task of four repeating pain stimulations and between two serial pain tasks separated by a 4-min interval was examined to determine whether signal attenuation may significantly confound pain investigations. METHODS: The characteristics of the brain activation of six subjects were determined using whole brain blood oxygenation level-dependent functional magnetic resonance imaging on a 1.5-T scanner. Tasks included both tingling and pain induced by transcutaneous electrical stimulation of the median nerve. The average group maps were analyzed by general linear modeling with corrected cluster P values of less than 0.05. The time courses of individual voxels were further investigated by analysis of variance with P values of less than 0.05. RESULTS: Significant differences between pain and tingling were found in the ipsilateral cerebellum, contralateral thalamus, secondary somatosensory cortex, primary somatosensory cortex, and anterior cingulate cortex. Highly significant signal decay was found to exist across each single pain task, but the signal was found to be restored after a 4-min rest period. CONCLUSIONS: This work shows that serial pain tasks can be used for functional magnetic resonance imaging studies using electrical nerve stimulation as a stimulus, as long as sufficient time is allowed between the two tasks.

Unsuspected temporomandibular joint pathology leading to a difficult endotracheal intubation.

A 40-yr-old woman with an unremarkable medical history and no prior surgeries presented for ambulatory surgery. Physical examination revealed normal jaw opening. On induction of general anesthesia, her jaw was found to be locked in a nearly closed position. We discuss anesthetic considerations and the pathology of temporomandibular joint anterior disk dislocation without reduction. A simple maneuver to reduce the dislocation is described.