Can short-term heart rate variability be used to monitor fentanyl-midazolam induced changes in ANS preceding respiratory depression?

Opioids have an occasional but high-risk side effect of respiratory depression. The detection of critical respiratory depression usually occurs after the event. Earlier detection would be beneficial in preventing increased morbidity and mortality of 0.01 % patients receiving analgesic opioids. Airway patency during inspiration requires vagal modulation. Regulation of the cardiovascular and respiratory centres may be coupled with a central mechanism that is indirectly measurable with heart rate variability (HRV). While opioids tend to increase parasympathetic tone, a decrease in airway stability could be due to a decrease in respiratory parasympathetic activity. Sympathetic arousal generated by apneic events may separately be recognised with short-term HRV. This pilot observational study examined the dynamic sympathovagal changes during fentanyl-midazolam induced respiratory depression on 10 subjects scheduled for minor surgery. A selection of HRV indices, able to work over sub-minute periods on non-stationary signals, were applied including a range of less common indices. Three analyses tested the effects: post-fentanyl, preceding the first central depression, and preceding obstruction of the upper airway. Statistical significance was assessed with overlap of bootstrap percentile confidence intervals for the median. A decrease in total variability, Lomb Total using the Lomb-Scargle method, is a positive finding for short-term HRV use in this study. No significant change before critical respiratory events was observed in traditional, spectral power, respiratory or other indices. One index, PolVar20, indicated a burst of sympathetic activity preceding respiratory depression similar to sleep apnoea arousals that restore airway patency. Before its usefulness in early detection of airway tone can be determined, PolVar20 requires further work: a statistical method for highly skewed distributions, auto adjustment for baseline variability, and detecting a range of sympathetic responses to apnea.

Heart rate variability indices for very short-term (30 beat) analysis. Part 1: survey and toolbox.

Heart rate variability (HRV) analysis over very short (<60 s) periods may be useful for monitoring dynamic changes in autonomic nervous system activity where steady-state conditions are not maintained (e.g. during drug administration, or the start or end of exercise). From the 1980s there has been a wealth of HRV indices produced in the quest for better measures of the change in parasympathetic and sympathetic activity. Many of the indices have been sparingly used and have not been investigated for application to short-term use. This study surveyed published methods of HRV analysis searching for indices that could be applied to very short time HRV analysis. The survey included measures of time domain, frequency domain, respiratory sinus arrhythmia, Poincaré plot, and heart rate characteristics. Indices were tested with short segments of archived data to remove those that produced invalid results, or were mathematically equivalent to, but less well known than other indices. The survey identified a comprehensive list of 115 indices that were subsequently coded and screened. Of these, 70 were unique and produced a finite number with 60 s data, so are included in the Toolbox. These indices require validation against physiological data before they can be applied to short-term HRV analysis of cardiac autonomic nervous system activity.

Heart rate variability indices for very short-term (30 beat) analysis. Part 2: validation.

Heart rate variability (HRV) analysis over shorter periods may be useful for monitoring dynamic changes in autonomic nervous system activity where steady-state conditions are not maintained (e.g. during drug administration, or the start or end of exercise). This study undertakes a validation of 70 HRV indices that have previously been identified as possible for short-term use. The indices were validated over 10 × 30 beat windows using PhysioNet databases with physiological states of rest, active, exercising, sleeping, and meditating (N from 12 to 20). Baseline 95 % confidence intervals of the median were established with bootstrap resampling (10,000x). Statistical significance was assessed using the overlap of 95 % confidence intervals. Thirty-one indices could differentiate between resting and at least one physiological state using 30 beat windows. All respiratory sinus arrhythmia indices and Poincaré plot indices were strongly correlated to time domain measures (SDNN or RMSSD). Spectral indices using the Lomb-Scargle algorithm were able to correctly identify paradoxical shifts in power with meditation and reduced power in exercise. Some less-known indices gave interesting results: PolVar20 identified the higher sympathetic activity of exercise with the largest positive magnitude. These indices should now be considered for rigorous gold standard tests with pharmacological blockade.

A new part task trainer for teaching and learning confirmation of endotracheal intubation.

Endotracheal intubation is a skill employed by a diverse range of healthcare professionals in a wide variety of circumstances. Failure to put this tube in the right place (in the trachea) can result in serious injury and death. There are a wide variety of methods for verification of proper placement. Some are more widely accepted than others. A universal guideline should be adopted to allow consistent and safe practice in all situations by all who do this procedure. Training for endotracheal intubation must also include training in the verification methods. We have developed a new airway part-task trainer that allows the use of all of the methods of tube placement verification.

Symptoms and Clinical Findings in Primary Headache Syndrome Versus Chronic Rhinosinusitis.

BACKGROUND: Primary headache syndrome (PHS) patients frequently present to otolaryngologists with sinonasal complaints and diagnosis of chronic rhinosinusitis (CRS) due to symptomatic overlap. In this study, we compare demographic, subjective, and objective clinical findings of patients with PHS versus CRS. METHODS: We retrospectively reviewed a database of patients presenting to a single tertiary care Rhinology clinic from December 2011-July 2017. Sino-Nasal Outcome Test-22 (SNOT) scores and Lund-Kennedy endoscopy scores were obtained. Lund-MacKay CT scores were calculated, if available. Requirement of headache specialist management was compared between PHS and CRS groups. Patients with both CRS and PHS (CRScPHS) that required headache specialist management were compared to patients with CRS without PHS (CRSsPHS) and patients with PHS alone using Kruskal-Wallis analysis of variance. Receiver operating characteristic (ROC) analyses were carried out to determine significant diagnostic thresholds. RESULTS: One-hundred four PHS patients and 130 CRS patients were included. PHS patients (72.1%) were more likely than CRS patients to require headache specialist management (6.9%, p<0.0001). CRSsPHS patients had significantly higher Nasal domain scores compared to PHS patients (p = 0.042) but not compared to CRScPHS patients (p>0.99). CRScPHS (p = 0.0003) and PHS (p<0.0001) subgroups of patients had significantly higher Aural/Facial domain scores compared to CRSsPHS patients. PHS patients also had significantly higher Sleep domains scores compared to CRSsPHS patients (p<0.0001). Both CRScPHS and CRSsPHS subgroups had significantly higher nasal endoscopy scores (p<0.0001) and CT scores (p = 0.04 & p<0.0001, respectively) compared to the PHS group. Aural/Facial domain score of 4, nasal endoscopy score of 4, and CT score of 2 were found to be reliable diagnostic thresholds for absence of CRS. CONCLUSIONS: The SNOT-22 may be used to distinguish PHS from CRS based upon the Aural/Facial and Sleep domains. Patients with CRS have more severe Nasal domain scores and worse objective endoscopy and CT findings.

Metastatic Neuroblastoma Presenting as a Submandibular Mass with Mandibular Bone Involvement in a Three-Year-Old Child.

Although neuroblastoma is one of the most common extra-cranial tumors in the pediatric population, it is rarely seen as a metastasis to the mandibular bone. The following is a case report of a 3-year-old male who initially presented with a submandibular mass that was proven to be a poorly differentiated metastatic neuroblastoma through excisional biopsy. This report is one of the few case reports that demonstrates metastatic submandibular neuroblastoma with mandibular bone involvement in the pediatric population.

Evaluation of conventional training in Clinical Breast Examination (CBE).

BACKGROUND: Clinical Breast Examination (CBE) is the examination of a women's breasts by a healthcare professional, such as a breast surgeon, family physician or breast-care nurse who is trained to recognise many different types of abnormalities and warning signs in the breast [1]. CBE is particularly important in rural areas and developing countries who have limited access to technology such as mammography. CBE needs to be taught to health professionals like any other clinical skill used by medical professionals in the workplace. CBE in part involves palpation of the breast, that is, determining by touch which breast lumps are normal and which are suspicious in feeling. The gold standard for assessing tactile skills in CBE is seeing whether students can accurately identify and discriminate between different breast lumps also known as masses (IDBM) on actual patients in a clinical setting. However, this is not practical in a medical education setting. Usually the testing methods 'go through the motions' of feeling the breast as part of CBE. So the students' technique is examined either using unrealistic simulation models or using an intimate examination associate (IEA), an actor/volunteer who permits students to examine their intimate body parts such as breast or genitals for teaching purposes. These volunteers do not have any abnormalities so this teaching does not include the actual detection of suspicious lumps. We undertook a study of clinical skill with 10 medical students to examine different methods of assessing novice student clinical skills after a brief training in CBE. OBJECTIVES: This study aims to evaluate the effectiveness of current training and assessment of novice students in CBE and their capacity to identify and discriminate breast masses (IDBM) on actual patients. METHODS: We assessed each student's IDBM ability in an actual clinical situation, a breast clinic with a mixture of eight IEAs and one real patient with a large, easily palpable, putative breast cancer. We recruited 10 clinically inexperienced medical students, who were trained for 30 minutes by two breast surgeons using an IEA. Students were tested in a simulated clinical setting, a breast clinic where each examined 4 IEAs and one patient. The students were blind to who was the real patient and who was an IEA. Patients were examined by a breast surgeon in private prior to the commencement in the study. The breast surgeon recorded any clinical finding on the patients during the initial examination. The surgeon coached each patient on how to mark the students and showed the patient their results so the patients had a benchmark. After each examination was finished the students had four different assessments: 1) patients marked each student, 2) students were independently proctored - that is, marked by an expert, 3) students recorded their clinical findings and 4) students recorded how confident they were that they had the correct findings. Results from different kinds of student assessments were compared.RESULTSA chi-square test for independence between true positive or negative masses versus student-assessed positive or negative masses was not significant at alpha = .05. This means that there was no statistical association in the indication of positive or negative presence of masses versus whether such masses were actually present or absent. By comparison, experts (breast surgeons) were able to detect normal and abnormal breast masses by palpation alone 100% of the time and rate their confidence level as 'certain'. Unlike the experts, student self-reported confidence was unrelated to their competence score (CS). Proctoring was inversely related to the students' CS.CONCLUSIONSThe main conclusion is that novice students do not seem to be able to accurately detect breast masses in a clinical setting even after training. On the basis of these results, we believe that a comprehension component in the current CBE testing is needed in addition to the current methods of testing.

RNA Binding by the Campylobacter jejuni Post-transcriptional Regulator CsrA.

Campylobacter jejuni is a Gram-negative rod-shaped bacterium that commensally inhabits the intestinal tracts of livestock and birds, and which also persists in surface waters. C. jejuni is a leading cause of foodborne gastroenteritis, and these infections are sometimes associated with the development of post-infection sequelae such as Guillain-Barré Syndrome. Flagella are considered a primary virulence factor in C. jejuni, as these organelles are required for pathogenicity-related phenotypes including motility, biofilm formation, host cell interactions, and host colonization. The post-transcriptional regulator CsrA regulates the expression of the major flagellin FlaA by binding to flaA mRNA and repressing its translation. Additionally, CsrA has previously been shown to regulate 120-150 proteins involved in diverse cellular processes. The amino acid sequence of C. jejuni CsrA is significantly different from that of Escherichia coli CsrA, and no previous research has defined the amino acids of C. jejuni CsrA that are critical for RNA binding. In this study, we used in vitro SELEX to identify the consensus RNA sequence mAwGGAs to which C. jejuni CsrA binds with high affinity. We performed saturating site-directed mutagenesis on C. jejuni CsrA and assessed the regulatory activity of these mutant proteins, using a reporter system encoding the 5' untranslated region (5' UTR) upstream of flaA linked translationally to the C. jejuni astA gene. These assays allowed us to identify 19 amino acids that were involved in RNA binding by CsrA, with many but not all of these amino acids clustered in predicted beta strands that are involved in RNA binding by E. coli CsrA. Decreased flaA mRNA binding by mutant CsrA proteins L2A and A36V was confirmed by electrophoretic mobility shift assays. The majority of the amino acids implicated in RNA binding were conserved among diverse Campylobacter species.

Breast Cancer Detection: The Development and Pilot Study of a "Tactile Landscape" as a Standardized Testing Tool.

INTRODUCTION: There is still a need for competent breast lump detection palpation skills, especially in developing countries. Our goal is to design, develop, and establish a test to determine whether students can, by touch alone, identify and discriminate between a range of different simulated lesions at different adiposity levels. METHODS: Common lesions, breast cancers, and cysts were physically simulated and hidden in a test object referred to as the "tactile landscape" (TL). Ribs, intercostal muscle, and nodularity-normal anatomical features-increased their realistic complexity. Varying depths of features simulated varying degrees of adiposity. A testing protocol was created to determine the testee's ability to identify and discriminate different commonly occurring breast masses using palpation. Five experts (four breast surgeons and one general practitioner) and 20 inexperienced medical students were recruited and tested. Results were compared. RESULTS: The TL has been based on previously verified breast models and has softness similar to 53% of women's breasts and nodularity similar to 60% as assessed in a breast clinic by breast surgeons. The five experts indicated that the simulated lesions felt like those they might encounter in clinical practice and all of them identified the lesions and nonlesions hidden in the TL 100% correctly, thus indicating the value of the model. In contrast, only one student was able to identify all the lesions. One student identified none of them. The remaining students mean score was 65%. CONCLUSIONS: All students but one performed poorly in comparison to the experts. This indicates that the test could be useful to test students' ability to identify and discriminate breast masses. If successful, it will add previously missing capability to the mix of assessment instruments already used, thus potentially improving clinical breast examination training and assessment.

A 12-month audit of laryngeal mask airway (LMA) use in a South Australian ambulance service.

BACKGROUND: The aim of the study was to provide an accurate account of current practice of laryngeal mask airway (LMA) use within SA Ambulance Service (SAAS) and identify issues that could lead to constructive training for paramedics and improve clinical care and patient safety. MATERIALS AND METHODS: A clinical audit of LMA use within SAAS was registered with the Director of Clinical Governance at Flinders Medical Centre in South Australia. Data were collected prospectively in a state wide all inclusive study over 12 months (February 2006 to January 2007). The primary outcome variable we determined was successful insertion after one or two attempts. Secondary outcome measures were overall success rate and reasons for failure. RESULTS: Insertion of an LMA was attempted by 179 paramedical staff in 164 patients. Success after one or two attempts was obtained in 65% of patients (107/164). Overall success rate (any number of attempts) was 74% (121/164), of those 45% were on the first attempt, 20% on the second attempt and the remainder (9%) required three or more attempts to achieve successful insertion. Reported failures were ascribed to patient anatomy (13), technique (9), airway soiling (7), device (6), trismus (1), high Glasgow Coma Score (1), trauma (1) or unknown (5). CONCLUSION: This clinical audit provides a comprehensive account of LMA use within SA Ambulance Service. Although the current practice was found to be acceptable, these results are below those of comparable groups and should be improved upon.

Correlated Poincaré indices for measuring heart rate variability.

Poincaré indices are usually applied to HRV to summarise long data sets collected over 24 hrs. Many applications of HRV are interested in dynamic, short term changes (<1 min). This study uses Poincaré indices published through the 1990's to the present, to determine which of them are correlated over the short term (25 beats). Dynamic changes were observed in 12 subjects pre-operatively receiving fentanyl and midazolam sedation with ECG collected for 5 mins before and 5 mins after fentanyl administration. Poincaré indices with a strong correlation (r>0.85) between the indices for each of the 12 subjects (p<0.001) (particularly with the common measures SDNN, RMSSD, pNN50 and meanRR) were identified. These indices will not be used for further investigation of dynamic effects of fentanyl and midazolam, two sedative drugs used in anaesthesia and intensive care. Indices that proved less suitable for short term analysis (eg. presence of outliers, inability to produce a valid index with smaller number of beats) were also identified. A shortlist of Poincaré indices that do not correlate strongly with commonly used measures may prove interesting in determining dynamic characteristics of the effect of sedative drugs on autonomic nervous system activity.

Comparison of three simulation-based training methods for management of medical emergencies.

Trainee medical officers (TMOs) participated in a study comparing three methods of simulation-based training to treat medical emergencies occurring in a hospital setting. The methods were: All groups had the same total teaching time. Participants (n=61) had an initial (pre-training) assessment by written tests, self assessment and simulations of medical emergencies ('VT' and 'HYPOglycaemia'). Participants were tested again post-training using similar simulations to the initial scenario and a new scenario ('ANAphylaxis'). Trained 'experts', blinded to the teaching group of participants, watched video-CDs of the simulations to assess participants' performance. All groups demonstrated increased knowledge and confidence (pre-training scores compared to post-training) but no differences could be detected between the three groups. In simulated emergencies, post-training scores were also improved. There was no difference between groups in the 'HYPO' scenario but in the 'VT' scenario there was moderate evidence that Group 3 was superior. In the 'ANA' scenario, Group 3 had far better test scores, especially in behavioural items. There did not appear to be any significant advantage of using whole body manikins over CSBT and simple part-task trainers. Full-mission simulation training helped develop the ability to recognise when skills learnt to manage one type of medical emergency can be useful in managing another emergency not previously encountered.

Assessing proficiency in adult basic life support: student and expert assessment and the impact of video recording.

Self-assessment is an important aspect in the development of lifelong learning skills for medical students, crucial to maintaining a high level of competence in practice. Basic Life Support (BLS) is a skill that all health professionals must acquire and maintain competence in. This paper reports data from a study of 95 first-year graduate entry medical students at Flinders University in Australia, determining how well the students could assess their own BLS performance. These students were videotaped performing a short CPR scenario using a Resusci Anne with SkillReporter (Laerdal, Norway). Using a six-point descriptive ratings scale, students graded themselves twice: once immediately after completing the task, and again after viewing a video of their performance. A single expert assessor viewed all the video recordings and, based on International Liaison Committee on Resuscitation (ILCOR) Guidelines, graded the students using the same scale. The hypothesis was that the intervention of viewing their performance on video would improve the correlation of their ratings with the expert assessor. The results showed that the students' assessments did not agree with the expert assessor either before (weighted kappa = 0.03) or after seeing the video (weighted kappa = 0.002). Possible reasons, including student attitudes and lack of benchmarking, are discussed. Self-assessment skills of students warrant further attention.

Randomized comparison of the SLIPA (Streamlined Liner of the Pharynx Airway) and the SS-LM (Soft Seal Laryngeal Mask) by medical students.

OBJECTIVE: The aim of the study was to compare the Streamlined Liner of the Pharynx Airway (SLIPA; Hudson RCI), a new supraglottic airway device, with the Soft Seal Laryngeal Mask (SS-LM; Portex) when used by novices. METHODS: Thirty-six medical students with no previous airway experience, received manikin training in the use of the SLIPA and the SS-LM. Once proficient, the students inserted each device in randomized sequence, in two separate patients in the operating theatre. Only two insertion attempts per patient were allowed. Students were assessed in terms of: device preference; success or failure; success at first attempt and time to ventilation. RESULTS: Sixty-seven per cent of the students preferred to use the SLIPA (95% confidence interval 49-81%). The SLIPA was successfully inserted (one or two attempts) in 94% of patients (34/36) and the SS-LM in 89% (32/36) (P = 0.39). First attempt success rates were 83% (30/36) and 67% (24/36) in the SLIPA and SS-LM, respectively (P = 0.10). Median time to ventilation was shorter with the SLIPA (40.6 s) than with the SS-LM (66.9 s) when it was the first device used (P = 0.004), but times were similar when inserting the second device (43.8 s vs 42.9 s) (P = 0.75). CONCLUSIONS: In the present study novice users demonstrated high success rates with both devices. The SLIPA group achieved shorter times to ventilation when it was the first device they inserted, which might prove to be of clinical significance, particularly in resuscitation attempts. Although the Laryngeal Mask has gained wide recognition for use by both novice users and as a rescue airway in failed intubation, the data presented here suggest that the SLIPA might also prove useful in these areas.

EyeSim--an ophthalmic response simulator.

This paper pertains to the design, construction and development of an ophthalmic response simulator, intended to augment current neurological examination teaching practices in medical schools. Neurological examination of the eyes informs a practitioner of the functional state of certain cranial nerves (II, III, IV and VI) through the assessment of visual acuity, visual fields, ocular movements, external and internal eye structures and ophthalmoscopic examination. For the medical student, the interpretation of these indicators may be difficult, compounded by the infrequence with which such patients may be presented. As such, the need was identified for a simulator capable of replicating the ophthalmic response of patients with typical and a range of atypical neurologies. Such a simulator could be used as a stand-alone device or developed toward inclusion in pre-existing, life-size, hi-fidelity mannequins. Specifically, EyeSim will be able to track the movements of a pen-torch and vary the apparent dilation of an iris in response to changing levels of illumination. These responses can then be modulated to reflect certain deficits that neural pathologies may cause. At present the simulator comprises the electrical, electronic and mechanical components that replicate the pupillary response of the iris and the motility of the ocular muscles, a computer for the reception and analysis of a video signal and the micro-controller components, which determine the action of the physical components based on an array of inputs.

Postoperative pain therapy: a survey of patients' expectations and their experiences.

For 2 months elective surgical patients (n = 259) were asked preoperatively about their expectations of pain and pain relief. At both 24 and 72 h after their surgery they were asked about their pain and pain control. The analgesics they received were monitored for the first 72 h. The survey revealed that patients do not have the necessary knowledge about pain relief to contribute effectively in their own pain management. Analgesics administered intermittently were generally effective when given, however, the dosing interval was too long for the agents used resulting in frequent reports of poor pain relief. We conclude that patients need better education on postoperative pain control therapy. Medical staff could prescribe, and nursing staff administer, analgesics more effectively.

Antinociceptive and motor effects of intrathecal morphine combined with intrathecal clonidine, noradrenaline, carbachol or midazolam in rats.

This study investigated antinociceptive effects of intrathecal morphine combined with intrathecal clonidine, noradrenaline, carbachol or midazolam in rats. Each animal received intrathecally, on 3 separate occasions (i) 2 micrograms morphine (M), (ii) a dose (D) of one of the non-opioid drugs, and (iii) a combination, 1/2(M+D), consisting of 1 microgram morphine plus half the dose of the non-opioid drug. Antinociceptive effects were assessed by the hot-plate and tail-flick tests over the duration of drug action. All non-opioid drugs studied led to dose-related antinociceptive effects when given alone. Addition of morphine caused a left shift in the dose-response curves of all the non-opioid drugs, indicating at least some degree of additive effects. Effects were considered supra-additive when the effect of the combination, 1/2(M+D), was significantly greater than both the effect of 2 micrograms morphine and the dose of non-opioid. Evidence of supra-additive antinociceptive effects was obtained only with the clonidine-morphine combination.

The efficacy of transdermal fentanyl in the treatment of postoperative pain: a double-blind comparison of fentanyl and placebo systems.

Forty consenting patients scheduled for abdominal surgery were entered into a double-blind comparison of the efficacy of transdermal fentanyl (TTS-fentanyl) and placebo (TTS-placebo) in the treatment of postoperative pain. All patients were allowed supplementary pethidine (25-50 mg) if pain relief was inadequate provided that their respiratory rate was greater than 10 breaths/min and there was no pronounced CNS depression. Visual analogue pain scores (VAPS), sedation rating scores (SRS), blood samples for the determination of fentanyl concentration, blood pressure, pulse and respiratory rate were determined hourly for 48 h from the time of TTS system application. The first lot of TTS systems were removed after 24 h and a second lot were applied which remained in situ for a further 24 h. There was no significant difference between the patients in the TTS-fentanyl and TTS-placebo groups in the VAPS throughout the 0-12, 12-24, 24-36 and 36-48 h periods suggesting that the quality of pain relief was similar between the 2 groups. However, significantly less supplementary pethidine was administered to the TTS-fentanyl group in the 12-24, 24-36 and 36-48 h periods. In contrast, the amount of supplementary pethidine administered in the 0-12 h period was similar in both groups which was consistent with the long delay time (mean +/- S.D. value of 16.6 +/- 10 h) before clinically effective concentrations of fentanyl were obtained from the systems. The profile of side effects was similar in the 2 groups.(ABSTRACT TRUNCATED AT 250 WORDS)