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Anesthesiology Jun 2019Opioids are a mainstay of perioperative analgesia. Opioid use in children with obstructive sleep apnea is challenging because of assumptions for increased opioid...
BACKGROUND
Opioids are a mainstay of perioperative analgesia. Opioid use in children with obstructive sleep apnea is challenging because of assumptions for increased opioid sensitivity and assumed risk for opioid-induced respiratory depression compared to children without obstructive sleep apnea. These assumptions have not been rigorously tested. This investigation tested the hypothesis that children with obstructive sleep apnea have an increased pharmacodynamic sensitivity to the miotic and respiratory depressant effects of the prototypic μ-opioid agonist remifentanil.
METHODS
Children (8 to 14 yr) with or without obstructive sleep apnea were administered a 15-min, fixed-rate remifentanil infusion (0.05, 0.1, or 0.15 μg · kg · min). Each dose group had five patients with and five without obstructive sleep apnea. Plasma remifentanil concentrations were measured by tandem liquid chromatography mass spectrometry. Remifentanil effects were measured via miosis, respiratory rate, and end-expired carbon dioxide. Remifentanil pharmacodynamics (miosis vs. plasma concentration) were compared in children with or without obstructive sleep apnea.
RESULTS
Remifentanil administration resulted in miosis in both non-obstructive sleep apnea and obstructive sleep apnea patients. No differences in the relationship between remifentanil concentration and miosis were seen between the two groups at any of the doses administered. The administered dose of remifentanil did not affect respiratory rate or end-expired carbon dioxide in either group.
CONCLUSIONS
No differences in the remifentanil concentration-miosis relation were seen in children with or without obstructive sleep apnea. The dose and duration of remifentanil administered did not alter ventilatory parameters in either group.
Topics: Adolescent; Analgesics, Opioid; Child; Dose-Response Relationship, Drug; Female; Humans; Infusions, Intravenous; Male; Miosis; Remifentanil; Sleep Apnea, Obstructive
PubMed: 30870164
DOI: 10.1097/ALN.0000000000002664 -
Neurology Jul 2021To determine the molecular basis of a new monogenetic recessive disorder that results in familial autonomic ganglionopathy with diffuse autonomic failure. (Clinical Trial)
Clinical Trial
OBJECTIVE
To determine the molecular basis of a new monogenetic recessive disorder that results in familial autonomic ganglionopathy with diffuse autonomic failure.
METHODS
Two adult siblings from one family (I-4 and I-5) and another participant from a second family (II-3) presented with severe neurogenic orthostatic hypotension (nOH), small nonreactive pupils, and constipation. All 3 affected members had low norepinephrine levels and diffuse panautonomic failure.
RESULTS
Whole exome sequencing of DNA from I-4 and I-5 showed compound heterozygosity for c.907_908delCT (p.L303Dfs*115)/c.688 G>A (p.D230N) pathologic variants in the acetylcholine receptor, neuronal nicotinic, α3 subunit gene (). II-3 from the second family was homozygous for the same frameshift (fs) variant (p.L303Dfs*115//p.L303Dfs*115). encodes a critical subunit of the nicotinic acetylcholine receptors (nAChRs) responsible for fast synaptic transmission in the autonomic ganglia. The fs variant is clearly pathogenic and the p.D230N variant is predicted to be damaging (SIFT)/probably damaging (PolyPhen2). The p.D230N variant lies on the interface between CHRNA3 and other nAChR subunits based on structural modeling and is predicted to destabilize the nAChR pentameric complex.
CONCLUSIONS
We report a novel genetic disease that affected 3 individuals from 2 unrelated families who presented with severe nOH, miosis, and constipation. These patients had rare pathologic variants in the gene that cosegregate with and are predicted to be the likely cause of their diffuse panautonomic failure.
Topics: Adolescent; Adult; Autonomic Nervous System Diseases; Constipation; Female; Genes, Recessive; Humans; Hypotension, Orthostatic; Male; Miosis; Mutation; Pedigree; Receptors, Nicotinic; Exome Sequencing
PubMed: 33947782
DOI: 10.1212/WNL.0000000000012143 -
Medecine Sciences : M/S Nov 2018Calcium (Ca) is an essential regulator for a large number of cellular functions in various tissues and organs, and small disturbances of Ca homeostasis can severely...
Calcium (Ca) is an essential regulator for a large number of cellular functions in various tissues and organs, and small disturbances of Ca homeostasis can severely compromise normal physiology. Intracellular Ca balance is mainly controlled by the reticular Ca sensor STIM1 and the plasma membrane Ca channel ORAI1 through a mechanism known as store-operated Ca entry (SOCE). Gain-of-function mutations in STIM1 or ORAI1 cause excessive extracellular Ca influx, resulting in tubular aggregate myopathy (TAM) and Stormorken syndrome (STRMK). Both disorders are spectra of the same disease and involve muscle weakness, miosis, thrombocytopenia, hyposplenism, ichthyosis, dyslexia, and short stature. Here we summarize the clinical and histological characteristics of both disorders, provide an overview on the genetic causes, and recapitulate the current knowledge on the pathomechanisms leading to the multi-systemic phenotype of tubular aggregate myopathy and Stormorken syndrome.
Topics: Biopsy; Blood Platelet Disorders; Calcium; Dyslexia; Erythrocytes, Abnormal; Genotype; Humans; Ichthyosis; Migraine Disorders; Miosis; Muscle Fatigue; Muscles; Mutation; Myopathies, Structural, Congenital; Neoplasm Proteins; ORAI1 Protein; Phenotype; Spleen; Stromal Interaction Molecule 1
PubMed: 30418142
DOI: 10.1051/medsci/201834s208 -
Anales de Pediatria (Barcelona, Spain :... May 2015
Topics: Female; Horner Syndrome; Humans; Infant, Newborn; Phenotype
PubMed: 25444033
DOI: 10.1016/j.anpedi.2014.10.024 -
Clinical Ophthalmology (Auckland, N.Z.) 2015The maintenance of mydriasis throughout cataract extraction surgery and the control of ocular inflammation are crucial for successful surgical outcomes. The development... (Review)
Review
The maintenance of mydriasis throughout cataract extraction surgery and the control of ocular inflammation are crucial for successful surgical outcomes. The development of miosis during cataract surgery compromises the visualization of the surgical field and working space for surgeons. This may lead to complications that include posterior capsular tear and associated vitreous loss, longer surgical time, and postoperative inflammation. Postoperative inflammation is often uncomfortable and frustrating for patients. It causes pain, redness, and photophobia. This compromises the best-uncorrected vision following surgery and often leads to multiple clinic visits. This article examines the literature published on the current treatments used to manage mydriasis, pain, and inflammation in cataract extraction surgery. Combination phenylephrine/ketorolac injection offers an exciting new class of medication for use in cataract surgery. With the recent approval of Omidria™ (combination of phenylephrine 1% and ketorolac 0.3%) by the US Food and Drug Administration (FDA) for intraocular use, we review the clinical utility of this new combination injection in cataract surgery. PubMed, MEDLINE, and conference proceedings were searched for the relevant literature using a combination of the following search terms: cataract extraction surgery, pupil dilation (mydriasis), miosis, phenylephrine, ketorolac, Omidria™, intracameral mydriatic. Relevant articles were reviewed and their references checked for further relevant literature. All abstracts were reviewed and full texts retrieved where available.
PubMed: 26203214
DOI: 10.2147/OPTH.S72321 -
Journal of Thrombosis and Haemostasis :... Sep 2019
Topics: Awards and Prizes; Blood Platelet Disorders; Dyslexia; Education, Medical; Erythrocytes, Abnormal; Hematology; History, 20th Century; History, 21st Century; Ichthyosis; Migraine Disorders; Military Medicine; Miosis; Muscle Fatigue; Norway; Research; Spleen; Veterinary Medicine
PubMed: 31479185
DOI: 10.1111/jth.14585 -
Indian Journal of Ophthalmology Dec 2017This paper presents the review of historical aspects and the current state-of-the-art in various pupil dilatation methods to be used in cataract surgery. The surgical... (Review)
Review
This paper presents the review of historical aspects and the current state-of-the-art in various pupil dilatation methods to be used in cataract surgery. The surgical algorithm in managing small pupil cases should include topical and intraocular mydriatics, appropriately selected viscosurgical device and mechanical dilatation with instruments, iris hooks, and/or pupil expanders.
Topics: Cataract; Cataract Extraction; Equipment Design; Humans; Miosis; Surgical Instruments
PubMed: 29208812
DOI: 10.4103/ijo.IJO_800_17 -
Journal of Vascular Surgery Aug 2022Surgery for neurogenic thoracic outlet syndrome (NTOS) has shown good outcome in numerous case series. However, 5% to 30% of patients will have persistent or recurrent...
OBJECTIVES
Surgery for neurogenic thoracic outlet syndrome (NTOS) has shown good outcome in numerous case series. However, 5% to 30% of patients will have persistent or recurrent symptoms, caused by incomplete first rib resection, reattachment of residual scalene muscle, fibrous scarring around the brachial plexus, or a wrong NTOS diagnosis. In patients with a sound diagnosis of recurrent or persisting NTOS, not responding to conservative measures, a secondary procedure can be considered. We report the results of redo thoracic outlet decompression surgery through the supraclavicular approach (SC-REDO-TOD) for persistent or recurrent NTOS.
METHODS
A retrospective review of a prospective database was performed. Every patient referred from September 2016 until January 2020 was eligible for inclusion. In an SC-REDO-TOD, we perform complete (cartilage-cartilage) resection of the first rib, any bony and fibrous anomalies, complete anterior and middle scalenectomy, and complete neurolysis of the brachial plexus (complete anatomical decompression of the brachial plexus). Clinical outcomes were assessed by questionnaires including the Disability of Arm, Shoulder and Hand (DASH), Cervico-Brachial Symptoms Questionnaire (CBSQ), and TOS (thoracic outlet syndrome) Disability scale.
RESULTS
In total, 45 patients had a SC-REDO-TOD. The median duration of hospital admission after SC-REDO-TOD was 1.41 days (interquartile range, 1.00 day). In total, 30 (66.66%) of 45 patients had recurrent NTOS, and 15 (33.33%) of 45 patients had persisting NTOS. Postoperative complications were seen in eight patients (18.18%). One patient had postoperative complications with permanent impairment (Horner syndrome). Seven patients had postoperative complications with full recovery (three patients had a chylous leakage that was treated with a median-chain triglycerides diet for 6 weeks, three patients had transient phrenic nerve palsy with full recovery <6 weeks, and one patient had a discrete Horner syndrome that resolved in 6 weeks). The median time of follow-up was 19.50 months (interquartile range, 14.00 months) and the response rate to the questionnaires was 91.11% at 6 months and 64.44% at 12 months. We found a positive and statistically significant difference for DASH score, CBSQ score, and TOS Disability Scale score comparing scores for all patients. (DASH score: P < .001; CBSQ score: P < .001; TOS Disability Scale: P < .001). Patients with first rib remnants showed a significant better response (lower DASH, CBSQ and TOS Disability Scale scores) compared with patients without first rib remnants (DASH score: P = .004; CBSQ score: P ≤ .014; TOS Disability Scale: P = .009).
CONCLUSIONS
SC-REDO-TOD after a previous NTOS surgery shows good results with a low risk of permanent impairment. Patients with NTOS with first rib remnants after primary surgery seem to benefit the most from SC-REDO-TOD surgery.
Topics: Decompression, Surgical; Horner Syndrome; Humans; Postoperative Complications; Retrospective Studies; Thoracic Outlet Syndrome; Treatment Outcome
PubMed: 35367561
DOI: 10.1016/j.jvs.2022.03.863 -
Acta Neurochirurgica Jun 2023There is an urgent need for easy-to-perform bedside measures to detect residual consciousness in clinically unresponsive patients with acute brain injury. Interestingly,...
BACKGROUND
There is an urgent need for easy-to-perform bedside measures to detect residual consciousness in clinically unresponsive patients with acute brain injury. Interestingly, the sympathetic control of pupil size is thought to be lost in states of unconsciousness. We therefore hypothesized that administration of brimonidine (an alpha-2-adrenergic agonist) eye drops into one eye should produce a pharmacologic Horner's syndrome if the clinically unresponsive patient is conscious, but not if the patient is unconscious. Here, in a first step to explore this hypothesis, we investigated the potential of brimonidine eye drops to distinguish preserved sympathetic pupillary function in awake volunteers from impairment of sympathetic tone in patients in a coma.
METHODS
We enrolled comatose patients admitted for acute brain injury to one of the intensive care units (ICU) of a tertiary referral center, in whom EEG and/or neuroimaging for all practical purposes had ruled out residual consciousness. Exclusion criteria were deep sedation, medications with known drug interactions with brimonidine, and a history of eye disease. Age- and sex-matched healthy and awake volunteers served as controls. We measured pupils of both eyes, under scotopic conditions, at baseline and five times 5-120 min after administering brimonidine into the right eye, using automated pupillometry. Primary outcomes were miosis and anisocoria at the individual and group levels.
RESULTS
We included 15 comatose ICU patients (seven women, mean age 59 ± 13.8 years) and 15 controls (seven women, mean age 55 ± 16.3 years). At 30 min, miosis and anisocoria were seen in all 15 controls (mean difference between the brimonidine-treated pupil and the control pupil: - 1.31 mm, 95% CI [- 1.51; - 1.11], p < 0.001), but in none (p < 0.001) of the 15 ICU patients (mean difference: 0.09 mm, 95% CI [- 0.12;0.30], p > 0.99). This effect was unchanged after 120 min and remained robust in sensitivity analyses correcting for baseline pupil size, age, and room illuminance.
CONCLUSION
In this proof-of-principle study, brimonidine eye drops produced anisocoria in awake volunteers but not in comatose patients with brain injury. This suggests that automated pupillometry after administration of brimonidine can distinguish between the extremes of the spectrum of consciousness (i.e., fully conscious vs. deeply comatose). A larger study testing the "intermediate zone" of disorders of consciousness in the ICU seems warranted.
Topics: Humans; Female; Middle Aged; Aged; Adult; Brimonidine Tartrate; Coma; Anisocoria; Ophthalmic Solutions; Miosis; Brain Injuries
PubMed: 37014450
DOI: 10.1007/s00701-023-05569-8 -
Eye (London, England) Aug 2022To evaluate static pupillometric measurements and making inter-ocular comparative analysis in healthy subjects for demonstrating the prevalance of physiological...
BACKGROUND
To evaluate static pupillometric measurements and making inter-ocular comparative analysis in healthy subjects for demonstrating the prevalance of physiological anisocoria in various lighting conditions and to compare the variations of the dynamic pupillometric measurements of the patients with physiological anisocoria.
METHODS
Automatic quantitative pupillometry system was used to measure pupillary diameters in low mesopic (0.1 cd/m), high mesopic (1 cd/m), low photopic (10 cd/m) and high photopic (100 cd/m) conditions. After inter-ocular comparison of these data, the prevalance of physiological anisocoria was detected in four different lighting conditions. The inter-ocular dynamic pupillometric parameters (amplitude, latency, duration and velocity of pupil contraction; latency, duration and velocity of pupil dilation) of these patients were further analysed.
RESULTS
After inter-ocular comparison of pupillary diameters of 195 participants [96 females (49.2%) and 99 males (50.8%)] with a mean age of 38.4 ± 18.9 years (range 7-78 years), six (3.1%) participants under high photopic; 11 (5.6%) participants under low photopic; 25 (12.8%) participants under high mesopic, and 34 (17.4%) participants under low mesopic illumination levels exhibited physiological anisocoria. The mean relative amplitude of anisocoric small pupils' contraction was lower than the mean relative amplitudes of pupil contraction of both isocoric and anisocoric large pupils (p = 0.021, p = 0.035, respectively). The mean velocity of anisocoric small pupils' contraction was lower than the mean velocity of anisocoric large pupils' contraction (p = 0.013).
CONCLUSIONS
The mean contraction amplitude and contraction velocity of smaller pupils was lower when compared to fellow larger pupils of anisocoric patients.
Topics: Adolescent; Adult; Aged; Anisocoria; Child; Female; Humans; Lighting; Male; Middle Aged; Miosis; Photic Stimulation; Pupil; Young Adult
PubMed: 34290440
DOI: 10.1038/s41433-021-01696-7