Morphine Sedation Research Articles

L-cysteine ethylester reverses the adverse effects of morphine on breathing and arterial blood-gas chemistry while minimally affecting antinociception in unanesthetized rats

L-cysteine ethylester (L-CYSee) is a membrane-permeable analogue of L-cysteine with a variety of pharmacological effects. The purpose of this study was to determine the effects of L-CYSee on morphine-induced changes in ventilation, arterial-blood gas (ABG) chemistry, Alveolar-arterial (A-a) gradient (i.e., a measure of the index of alveolar gas-exchange), antinociception and sedation in male Sprague Dawley rats. An injection of morphine (10 mg/kg, IV) produced adverse effects on breathing, including sustained decreases in minute ventilation. L-CYSee (500 μmol/kg, IV) given 15 min later immediately reversed the actions of morphine. Another injection of L-CYSee (500 μmol/kg, IV) after 15 min elicited more pronounced excitatory ventilatory responses. L-CYSee (250 or 500 μmol/kg, IV) elicited a rapid and prolonged reversal of the actions of morphine (10 mg/kg, IV) on ABG chemistry (pH, pCO2, pO2, sO2) and A-a gradient. L-serine ethylester (an oxygen atom replaces the sulfur; 500 μmol/kg, IV), was ineffective in all studies. L-CYSee (500 μmol/kg, IV) did not alter morphine (10 mg/kg, IV)-induced sedation, but slightly reduced the overall duration of morphine (5 or 10 mg/kg, IV)-induced analgesia. In summary, L-CYSee rapidly overcame the effects of morphine on breathing and alveolar gas-exchange, while not affecting morphine sedation or early-stage analgesia. The mechanisms by which L-CYSee modulates morphine depression of breathing are unknown, but appear to require thiol-dependent processes.

Síndrome torácica aguda em paciente escolar com doença falciforme: um relato de caso

OBJECTIVE: To describe the case of a male pediatric patient with acute thoracic syndrome (ATS) in sickle cell anemia, linking it to the medical literature. CASE DESCRIPTION: A 9-year-old male patient, developed strong pain associated to headache and priapism, hence admitted to the emergency of a tertiary referral hospital. A priapism relief was noticed after hydration and morphine sedation. He developed severe acute thoracic syndrome, pneumonia and pleural effusion. The use of cefotaxime, clindamycin and clarithromycin was started. Mechanical ventilation was necessary and the patient was sent to the intensive care unit. On the tenth day, patient developed sepsis consequently cefotaxime and clindamycin were interrupted and piperacilin + tazobactam + linezoline were introduced. Kept clarithromycin. On the twelfth day, he had prophylaxis for pulmonary thromboembolism (TEP) with enoxaparin due to the expanded D-dimer. A second TEP was confirmed after some days. Three blood transfusions were needed during the hospitalization. He recovered gradually and was discharged on the thirty-sixth day keeping on thromboembolism prophylaxis until his return for other tests. COMMENTS: Patient had the infection and pulmonary thromboembolism as possible causes to trigger the acute thoracic syndrome. As observed in the medical literature, the pain crises anticipated the ATS. Alterations were observed on the laboratorial tests and imaging exams compatible with cases described by other authors. The good progress was the reflex from the adequate diagnosis and treatment.

Rhinotheca Prosthesis in a Carcará (Caracara plancus)

Background: The bird’s beak is a structure in constant growth, covered by keratinized epidermal sheaths called rhamphotheca. When subjected to certain degrees of injury, birds can suffer from lesions and fractures in different parts of the body, including the beak. One can treat simple ranch lesions by antisepsis and covering it with resin while the keratin is replaced; yet in complete fractures, with segment avulsion, they need complex prostheses to restore the functions of the nozzle. The main goal of this study was to report a case of a synthetic rhinotheca prosthesis placement in a wild carcará (Caracara plancus). Case: The carcará was referred to the Veterinary Medical Teaching Hospital of the UNIUBE, at the end of May 2018, by Uberaba’s Environmental Police, with a history of having been run over. On the physical examination, the animal showed aggressive behavior, low body weight, increased heart and respiratory rates, mild dehydration and complete fracture of the rhinotheca, with avulsion of the mid-distal portion and presence of necrosis in the remaining proximal remnant, the last one seen after debridement and complete cleansing of the lesion. In the following days, complementary exams were performed aiming a complete evaluation of the animal, these revealed the following: oral cavity swab, positive for Candida sp.; radiography of thoracic and pelvic limbs, without any changes; research of hemoparasites, with a negative result; and complete blood count showing marked leukocytosis. The animal was kept in the hospital’s wild animal ward, with a daily handling of 400 g of chicken neck and heart, processed on a blender and was also supplemented with a variety of minerals. After the wild animal was managed for eleven months, evolving to the ideal weight set for the species, the process for making the prosthesis started. At first, the prosthesis was made manually with epoxy resin and polyamide, being molded on the animal's rhinotheca, before that, the carcará was sedated with intranasal midazolam, and then modeled in the ideal shape for the beak. Then, the definitive prosthesis was made with acrylic resin, using the previous mold as a base. The surgical procedure was performed in April 2019, with an anesthetic protocol composed of midazolam, dexmedetomidine, ketamine and morphine for sedation, and maintenance in sevoflurane. Prosthesis and rhinotheca were both fixated by bilateral perforation with a 1.0 mm drill, and later on 2 titanium screws were inserted for dental use, these measuring 1.5 mm. After being correctly threated, the screws received a thin layer of acrylic resin on top, for better fixation. Immediately after the operation, the animal was able to use the prosthesis to feed itself. After the surgical procedure, the bird was destined for a sanctuary, and months later the prosthesis eventually fell. Since then, the bird has remained without it.Discussion: Because the beak did not grow due to trauma and consequent necrosis, and the animal did not adapt well with the remnant still present, the manufacture of the prosthesis was the solution so that it could return to its natural habits and behaviors. For greater adherence and fixation, we opted for the use of 2 titanium screws for dental use with the deposition of a thin layer of acrylic resin on top of both. Prostheses can be successful in fixing, but there are no studies indicating how long they will remain viable. Therefore, even with the success of the procedure, allowing the bird to return to its natural habits and behaviors, until after the fall of the prosthesis, it is an animal that needs to be kept in captivity suitable for daily observation. Keywords: raptors, wild animals, beak, rhinotheca, prosthesis, synthetic, rehabilitation. Descritores: rapinantes, animais selvagens, bico, rinoteca, prótese, sintética, reabilitação.

Adrenergic surge and hypertensive crisis after weaning from neurosedation in children

Pharmacological sedation in brain-injured patient is crucial to preserve intra-cerebral hemodynamic stability. Stopping sedation may be accompanied by a procession of clinical and psychic symptoms called withdrawal syndrome (WS) and secondary to an adrenergic discharge leading to tachycardia and possible relapse. We aimed to describe the incidence of these adrenergic surges and the evolution of the WS. Our retrospective study was carried out from April 2017 to March 2018 in the pediatric intensive care unit department of the 1st November University Hospital (61 patients included). Morphine derivatives and hypnotics (midazolam type) were used for sedation. Adrenergic discharge is defined by systolic-diastolic hypertension > 95th percentile in children, tachycardia, tachypnea, agitation. sociodemographic status, nature of brain injury, duration of sedation, duration of ventilation, time delay to withdraw sedation, time delay of clinical manifestations after WS. Fourteen patients (23%, 9 boys and 5 girls) evidenced a WS, mean age: 60.43 months-old. Children were admitted for isolated serious head injury ( n = 4), severe meningitis ( n = 2), cerebral aspergillosis ( n = 1), postoperative brain tumors ( n = 7). The morphine sedation duration was 6 ± 0.5 days; the duration of sedation with benzodiazepines was 7.1 ± 1.5 days. After the cessation of sedation, patients were ventilated ( n = 10), 2 patients had an intubation probe and 2 had a tracheotomy. The peak of the adrenergic surge was observed 7.5 ± 2.25 hours after cessation of sedation; the averaged systolic blood pressure was 165 mm Hg and the averaged diastolic blood pressure 107 mm Hg; the heart rate was 105 beats/min. Two patients evidencing a state of extreme agitation requiring reintroduction of benzodiazepines for less than 24 hours. The average duration of hospitalization was 12.8 days ± 6.3 days [6–22 days]. One patient died in a context of relapse of intracranial hypertension and perilesional edema. Stopping sedation in a brain-damaged patient leads to an adrenergic surge that may be responsible for an extension of hospitalization time in an intensive care unit. The cessation of sedation would be provided by a rigorous withdrawal protocol.

Effect of morphine combined with noninvasive positive pressure ventilation in the treatment of patients with acute left heart failure

Objective To investigate the effect of morphine combined with noninvasive positive pressure ventilation in the treatment of patients with acute left heart failure. Methods 80 patients with acute left heart failure were enrolled, and they were randomly divided into two groups according to the digital table method, 40 cases in each group.The patients in the control group were treated with noninvasive positive pressure mechanical ventilation.The patients in the observation group were treated with morphine sedation on the basis of the treatment of the control gorup.The vital signs test indicators, disease-related parameters, clinical events, cognitive function and quality of life were compared between the the two groups. Results The systolic blood pressure, heart rate, respiratory rate, PaCO2 and myocardial oxygen consumption in the observation group were significantly lower than those in the control group at 30min after treatment, PaO2 and pH in the observation group were significantly higher than those in the control group, the APACHEⅡ, BNP, Hs-cTnl and CK levels in the observation group at 24 h after treatment were significantly lower than those in the control group, the differences were statistically significant(t=8.349, 13.127, 7.413, 17.072, 15.334, 2.631, 3.088, 12.371, 8.061, 4.784, 18.931, 6.568, 9.464, all P 0.05]. Conclusion Morphine has significant influence on the effect of noninvasive positive pressure mechanical ventilation in patients with acute left heart failure. Key words: Heart failure; Ventilators, mechanical; Positive-pressure respiration; Morphine; Quality of life

Ventilation and the Response to Hypercapnia after Morphine in Opioid-naive and Opioid-tolerant Rats.

Opioid-related deaths are a leading cause of accidental death, with most occurring in patients receiving chronic pain therapy. Respiratory arrest is the usual cause of death, but mechanisms increasing that risk with increased length of treatment remain unclear. Repeated administration produces tolerance to opioid analgesia, prompting increased dosing, but depression of ventilation may not gain tolerance to the same degree. This study addresses differences in the degree to which chronic morphine (1) produces tolerance to ventilatory depression versus analgesia and (2) alters the magnitude and time course of ventilatory depression. Juvenile rats received subcutaneous morphine for 3 days (n = 116) or vehicle control (n = 119) and were then tested on day 4 following one of a range of morphine doses for (a) analgesia by paw withdraw from heat or (b) respiratory parameters by plethysmography-respirometry. Rats receiving chronic morphine showed significant tolerance to morphine sedation and analgesia (five times increased ED50). When sedation was achieved for all animals in a dose group (lowest effective doses: opioid-tolerant, 15 mg/kg; opioid-naive, 3 mg/kg), the opioid-tolerant showed similar magnitudes of depressed ventilation (-41.4 ± 7.0%, mean ± SD) and hypercapnic response (-80.9 ± 15.7%) as found for morphine-naive (-35.5 ± 16.9% and -67.7 ± 15.1%, respectively). Ventilation recovered due to tidal volume without recovery of respiratory rate or hypercapnic sensitivity and more slowly in morphine-tolerant. In rats, gaining tolerance to morphine analgesia does not reduce ventilatory depression effects when sedated and may inhibit recovery of ventilation.

Cardiac arrest from tramadol and fentanyl combination.

Sir, Tramadol is a centrally acting atypical opioid analgesic commonly used in the treatment of moderate to severe pain. It has a low affinity to μ opioid receptors and also inhibits the reuptake of serotonin and norepinephrine. Fentanyl is a potent, synthetic opioid with a rapid onset of action and strong affinity to μ receptor. Both the drugs are considered to have a high safety profile and used widely in anaesthesia. Fentanyl and tramadol impair presynaptic reuptake of serotonin and in combination with other serotonergic medications can cause serotonin syndrome. We report a case where premedication with the two drugs in therapeutic doses led to serotonin syndrome with severe life-threatening cardiac arrhythmia. A 43-year-old male American Society of Anaesthesiologists physical status1 patient, with radicular pain was scheduled for C5–6 anterior cervical discectomy. He was on gabapentin 150 mg tid and ibuprofen 200 mg bid for pain relief since 1 month. Preanaesthetic evaluation had been insignificant, and and so was the examination prior to shifting into the theatre. After connecting standard monitors and preoxygenation, intravenous (i.v.) fentanyl 50 μg (0.83 μg/kg, in dilution of 1 ml = 50 μg) was administered. Patient was agitating, and pain was thought to be the cause of his agitation. For the fear of developing chest wall, rigidity another agent was considered instead of higher doses of fentanyl. I.v. tramadol 75 mg (1.25 mg/kg, in dilution of 1 ml = 20 mg) was administered slowly over 2–3 min. Immediately a supraventricular rhythm (SVT) with a rate of 180/min and ventricular ectopics were noted on the monitor. It soon deteriorated to ventricular tachycardia (VT) and then into ventricular fibrillation (VF). Cardiopulmonary resuscitation (CPR) was initiated, and airway was secured with endotracheal intubation. Defibrillation with biphasic mode (200 J) was administered thrice during the CPR cycle without sustained sinus rhythm. Injection amiodarone 300 mg bolus was administered after 3rd shock after which sustained sinus rhythm was achieved. After initiating maintenance amiodarone infusion (0.5 mg/kg/h for 24 h) and vasoactive support (noradrenaline and adrenaline infusion at 20 mcg/min) patient was shifted to the intensive care unit (ICU). In the ICU, ventilation was continued for a day with midazolam and morphine for sedation and analgesia. A bedside echocardiogram revealed a good cardiac contractility and output. Induced hypothermia at 34°C was maintained for the day. The next day vasoactive drugs were weaned off, and the patient was awake and successfully extubated. Amiodarone was changed to oral mode of administration and patient was discharged to the ward on 2nd day. The combination of tramadol and fentanyl for premedication is seldom used. The combination has improved tolerance for awake endotracheal intubation[1] and has reduced the incidence of supraventricular arrhythmia in patients undergoing pulmonary resection.[2] Fentanyl associated fatalities have been primarily due to respiratory depression as even low concentrations lead to it.[3] Life-threatening central nervous system (CNS) and cardiac complications are generally found after tramadol ingestion at high doses with unintentional or intentional suicidal attempts. Ahmadi et al., after analysing the cases of tramadol intoxication found mortality rate of 0.97%. Most of the cases have been reported in conjunction with other drugs such as CNS depressants.[4] However, Shadnia et al., reported two fatalities with tramadol intoxication without any co-ingestions.[5] In therapeutic doses, both tramadol and fentanyl have been implicated in serotonin toxicity though tramadol is more notorious for severe toxicity.[6] Serotonin toxicity is marked by the triad of neuromuscular excitation, autonomic stimulation and changes in mental state. Based on the clinical profile we suspected serotonin syndrome to be causative for the complication in our patient. The features of toxicity from drug combination develop rapidly after onset of effective blood levels of the second drug. The autonomic features such as tachycardia and tachypnea are not usually severe.[6] In our patient, the administration of i.v. fentanyl initiated the toxicity features (agitation) which became more pronounced with tramadol dose. However, the cardiac signs erstwhile considered not to be of serious consequence, in our patient caused near fatal arrhythmia. The rhythm quickly transformed from SVT to VT and then to VF [Figure 1]. No role of use of gabapentin preoperatively in this peroperative drug interaction between fentanyl and tramadol could be explained. Figure 1 Electrocardiogram tracing of the rhythm during cardiopulmonary resuscitation To our knowledge and belief, this is the first report of serotonin toxicity with tramadol and fentanyl combination, in therapeutic doses without any other serotonergic medication. The inability to monitor serum drug level has been a limitation, but the absence of any other drug administered prior to fentanyl and tramadol effectively establishes the aetiology. This case report highlights the dangers of combining two drugs with potential of serotonin toxicity and the severity of cardiac complication that can even be near fatal.

Sedation management during therapeutic hypothermia for neonatal encephalopathy: Atropine premedication for endotracheal intubation causes a prolonged increase in heart rate

AimHeart rate (HR) plays an important role in the assessment of stress during therapeutic hypothermia (TH) for neonatal encephalopathy; we aimed to quantify the effect on HR of endotracheal (ET) intubation and drugs given to facilitate it. If atropine premedication independently increased HR, the main indicator of effective sedation, we hypothesised that increased sedation would have been given. MethodsThirty-two, term, neonates recruited into a randomised pilot study comparing TH and TH combined with 50% Xenon inhalation were studied. Indications for ET intubation included: resuscitation at delivery, clinical need and elective re-intubation with a cuffed ET tube if randomised to Xenon. Standard intubation drugs comprised one or more of intravenous morphine, atropine, and suxamethonium. Local cooling guidelines were followed including morphine infusion for sedation. ResultsAt postnatal hours five to eight atropine increased HR in a linear regression model (p<0.01). All other independent variables were excluded. Where more than one dose of atropine was given total morphine sedation given up to 8h into the treatment period was significantly higher (p<0.01). ConclusionWe have shown that atropine premedication for ET intubation significantly increased HR, the main indicator of effective sedation and total morphine dose for sedation during early TH was increased where more than one dose of atropine was given. Bradycardia was not reported in any neonate, even without atropine premedication. We suggest that the use of atropine as part of standard premedication for ET intubation of term neonates undergoing TH should be reconsidered.

Androgens and opiates

Abuse of anabolic androgenic steroids (AAS) and opioids intersects in athletics. Evidence from humans and animals suggests that AAS may act in the brain through opioidergic mechanisms, and may potentiate effects of opioids. To determine whether AAS enhance motivation for opioid intake, in this study, male rats were treated chronically for 6 weeks with high levels of testosterone (7.5 mg/kg) or vehicle subcutaneously, and they were tested for morphine self-administration under fixed-ratio (FR) and progressive-ratio (PR) schedules. Initially, rats received chronic morphine infusion (16.8-50 mg/kg/day) over 7 days. Subsequently, rats were tested for morphine self-administration (3.2 mg/kg) 6 h/day for 3 days under an FR1 schedule, and for 7 days under a PR 9-4 schedule. Under the FR1 schedule, controls self-administered more morphine (95.9±8.5 mg/kg) than testosterone-treated rats (63.2±7.2 mg/kg; P<0.05). Under the PR schedule, there was no effect of testosterone on morphine intake or operant responding (26.7±5.7 responses vs. 30.9±5.9 responses for vehicle; NS). To determine whether testosterone enhances morphine sedation, additional rats were treated with testosterone or vehicle and evaluated for locomotor behavior and rearing activity over 30 min in response to saline or 10 mg/kg morphine. Morphine inhibited locomotor activity and rearing; testosterone selectively reduced rearing behavior, but did not alter locomotor behavior. These results suggest that testosterone does not increase motivation for morphine.

The comparison of dexmedetomidine and morphine on respiratory mechanics in patients with chronic obstructive pulmonary disease during mechanical ventilation

Objective To study the effect of dexmedetomidine(DEX) and morphine hydrochloride on respiratory mechanics in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) undergoing mechanical ventilation.Methods Forty patients of AECOPD with respiratory failure undergoing mechanically ventilated were randomly divided into two groups (n=20).The control group were treated with morphine for sedation while the experimental group with DEX.APACHE Ⅱ score,bispectral index (BIS) score,ramsay score were recorded.Respiratory mechanical parameters after sedation,and changes in vital signs as well as blood gas were compared before and after sedation.Results Compared with the control group,the mean arterial pressure (MAP) and pulse in the experimental group were decreased after sedation[(80±3) mm Hg vs (75±4) mm Hg(1 mm Hg=0.133 kPa),(90±3) bpm vs (79±3) bpm](P＜0.01).The mean airway pressure(Paw) and plateau pressure(Pplat) were significantly downregulated in experimental group [(7.5±0.7) cm H2O vs (6.2±0.6) cm H2O (1 cm H2O=0.098 kPa),(19.8±1.7) cm H2O vs (18.0±1.1) cm H2O] (P＜0.05).peak esophageal pressure (PPEAK ES) and the peak esophageal manometry reference esophagus pressure difference (dPES) was increased [(-3.4±0.7) cm H2O vs (-5.4±1.0) cm H2O,(-6.9±1.0) cm H2O vs (-9.8±1.3) cm H2O] (P＜0.01).There were no significant difference between the two groups in folding screen the end of the suction gas during transpulmonary pressure (Ptp Plat) and pulmonary static compliance (Cst)[(25.5±2.3) cm H2O vs (26.0±2.6) cm H2O,(20.5±1.9)em H2O vs (20.1±1.2) cm H2O].The airway resistance (Raw)[(20.3±0.9) cm H2O·L-1·s-1 vs (15.6±1.4) cm H2O·L1·s-1](P＜0.01)and mechanical work of breathing (WOBv)[(0.49±0.10) j/L vs (0.43±0.06) j/L](P＜0.05) were increased.The patient work of breathing (WOBp) was significantly increased [(0.11 ±0.02)j/L vs (0.16±0.04)j/L] (P＜0.01).The time of mechanical ventilation and the intensive care unit (ICU)staying time were reduced [(76±5) h vs (64±3) h、(6.0±1.5) d vs (4.6±0.9) d](P＜0.05).Conclusions DEX increased the sedative effect and lung compliance,and decreased Raw in patients undergoing mechanical ventilation compared with morphine.DEX would also unload respiratory muscle oxygen consumption estimated by reducing the inspiratory load and work of breathing. Key words: Dexmedetomidine; Chronic obstructive pulmonary disease; Mechanical ventilation; Respiratory mechanics

Functional brain maturation assessed during early life correlates with anatomical brain maturation at term-equivalent age in preterm infants

Amplitude-integrated electroencephalogram (aEEG) is a reliable monitoring tool for electrocortical activity with good predictive value in preterm infants. Magnetic resonance imaging (MRI) is a good neuroimaging tool to detect brain lesions and to evaluate brain maturation. We hypothesized that early aEEG measures, recorded over the first 3 d of life in very preterm infants, correlate with brain maturation and injury score assessed by conventional MRI at term-equivalent age. Thirty-nine infants born at a mean (range) gestational age (GA) of 29.5 (27.0-31.9) wk and birth weight 1,230 (680-2,020) g had continuous aEEG during the first postnatal 72-84 h. aEEG maturity scores and average maximum and minimum amplitudes were evaluated. Conventional brain MRI was performed at 41.2 (37.1-44.1) wk postmenstrual age (PMA) on a 3T GE system and scored qualitatively for injury and maturation. The average aEEG total maturity score and its cycling subscore were positively and significantly associated with the total MRI maturation score after adjustment for GA, morphine sedation, and PMA at MRI examination. No association was found between the aEEG measures and the MRI injury scores. Early aEEG maturity seems to relate to structural MRI brain maturation at term-equivalent age in preterm infants.

Memories and post-traumatic stress-related symptoms in older, post-cardiac surgery patients: substudy of an RCT

The majority of ICU survivors display little evidence of severe psychological sequelae. However, there is evidence of post-traumatic stress disorder (PTSD)-related symptoms such as anxiety, depression, panic attacks, distressing memories and flashbacks within the first 3 months post ICU discharge [1,2]. This substudy of the DEXCOM trial 3 (randomised controlled trial of neurobehavioural effects of dexmedetomidine or morphine for sedation and analgesia in patients 60 years or older, undergoing coronary artery bypass grafting and/or valve replacement) aims to explore any negative memories of the ICU and development of PTSD-related symptoms between treatment groups of patients at high risk of developing delirium.

Pediatric Acute and Surgical Pain Management

Acute surgical pain management in children is best addressed by a dedicated pain management team. Although PCA with opioids forms the main modality of analgesia, regional techniques have gained popularity. PCA by proxy and PCA basal infusions enhance analgesia but carry a risk for respiratory depression and sedation. Efficient prevention of opioid-induced respiratory depression requires the use of appropriate monitoring including pulsoximetry and respiratory rate, clinical sedation scoring system, repeated assessment by the pain team, early intervention protocols, and use of nonopioid adjuncts like IV or oral acetaminophen and ketorolac/NSAIDs. Thalamocortical connections underpinning the neuroanatomy of pain appear between 20 and 30 weeks of gestational age, and the physiological mechanisms for pain perception become established by early second trimester. There are long-lasting effects of pain experienced in early life underscoring the need to treat surgical pain in fetuses, premature infants, and neonates. In contrast, there is a growing body of evidence in animal models implicating opioids in adversely altering neuronal proliferation in the developing brain and clinical studies where in morphine sedation in the neonatal period was found to decrease visual motor integration in childhood, suggesting a potential for neurocognitive sequelae. Ongoing research provides hope that future integration of pharmacogenetics, metabolomics, and proteomics in clinical decision and analgesic selection/dosing processes will maximize analgesia and minimize adverse effects.

Assessing the predictive value of the bispectral index vs patient state index on clinical assessment of sedation in postoperative cardiac surgery patients

Purpose To compare the depth of sedation determined by Ramsay sedation scale (RSS) with electroencephalogram-based bispectral index (BIS) and patient state index (PSI). Materials and Methods Fifty mechanically ventilated cardiac surgical patients undergoing propofol and morphine sedation were assessed hourly for up to 6 hours or until tracheal extubation using the BIS, PSI, and RSS. Correlation between RSS, BIS, and PSI was determined, as well as the interrater reliability of RSS, BIS, and PSI. κ statistics was used to further evaluate the agreement between BIS and PSI. Results There was positive correlation between BIS and PSI values ( ρ = 0.731, P < .001). The average weighted κ coefficient was .40 between the BIS and PSI, 0.28 between the RSS and BIS, and 0.16 between the RSS and PSI. Intraclass correlation was consistently higher between the BIS and PSI at all time intervals during the study. Logistic regression modeling over study duration showed that the BIS was consistently better at predicting oversedation (area under the curve, 0.92) than the PSI (area under the curve, 0.78). A comparison of BIS and PSI receiver operating characteristic curves showed that the BIS monitor was a better predictor of oversedation compared with the PSI ( P = .02). Conclusions There is significant positive correlation between the BIS and PSI but poor correlation and poor test agreement between the RSS and BIS as well as RSS and PSI. The BIS is a better predictor of oversedation compared with the PSI. There was no significant difference between the BIS and PSI with respect to the prediction of undersedation.

Behavioural and cardiorespiratory effects of a constant rate infusion of medetomidine and morphine for sedation during standing laparoscopy in horses

Standing surgical procedures are performed commonly in horses under sedation. This approach minimises the morbidity/mortality risks associated with general anaesthesia. The use of a medetomidine and morphine combination has not been investigated in horses despite the usefulness of each drug individually. To determine the efficacy of a medetomidine and morphine combination to produce standing sedation with minimal cardiorespiratory changes and adequate analgesia for exploratory laparascopy in mature horses. The combination of medetomidine and morphine will induce reliable sedation with minimal cardiorespiratory changes. Medetomidine (5 microg/kg bwt i.v.) followed in 10 min by morphine (50 microg/kg bwt i.v.) and 10 min later by a constant rate infusion (CRI) of medetomidine and morphine (5 and 30 microg/kg bwt/h, respectively) was administered in 7 horses undergoing standing exploratory laparoscopy. Quality of sedation and cardiorespiratory function were assessed. Sedation was satisfactory after the medetomidine and morphine bolus. The CRI of both drugs enhanced sedation and ataxia. Mean visual analogue scores on a scale of 10 varied between 7.8 and 8.8 and were similar between anaesthesiologists and surgeons. Heart rate, respiratory rate and packed cell volume (PCV) decreased significantly after medetomidine and, at some periods, during the CRI. Blood pressure only increased significantly at 5 min and arterial O2 decreased significantly at 10 min post medetomidine. PCV remained significantly lower and total protein decreased post morphine and CRI administration. Arterial CO2 increased towards the end of the CRI. Cardiac output did not change significantly over time. The combination of medetomidine and morphine results in reliable sedation and stable cardiorespiratory function in horses undergoing exploratory laparascopy.

The impact of delaying enteral feeding on gastric emptying, plasma cholecystokinin, and peptide YY concentrations in critically ill patients*

Enteral nutrient (EN) deprivation slows gastric emptying (GE) and increases plasma cholecystokinin (CCK) concentrations in healthy humans and may potentially contribute to the delayed GE in the critically ill. This study examined the impact of delayed feeding on GE, plasma CCK, and peptide YY (PYY) concentrations in the critically ill. Randomized controlled trial. Mixed medical and surgical intensive care unit (ICU). Twenty-eight critically ill patients were randomized to receive EN either within 24 hrs of admission ("early feeding": 54.9 +/- 3.3 yrs; Acute Physiology and Chronic Health Evaluation (APACHE) II = 23.0 +/- 1.8) or on day 4 of admission after GE assessment ("delayed feeding": 56.1 +/- 4.2 yrs, APACHE II = 21.7 +/- 1.8). GE of 100 ml of Ensure was measured using scintigraphy on day 4 of admission. Blood was sampled for measurement of plasma CCK, PYY, and glucose concentrations. Demographics, APACHE II score, use of inotrope and morphine sedation were similar between the groups. The mean administered/prescribed caloric ratio in the "early feeding" group was 72 +/- 4%. There were no differences in the retention of meal, intragastric meal distribution, proportion of patients with delayed GE (9/14 vs. 9/14), and plasma CCK and PYY concentrations during fasting and postprandially between the two groups. There was no relationship between the number of calories received and percentage of meal retention at 240 min (p > .05). However, delayed feeding was associated with longer duration of mechanical ventilations (13.7 +/- 1.9 vs. 9.2 +/- .9 days, p = .049) and length of stay in ICU (15.9 +/- 1.9 vs. 11.3 +/- 0.8 days, p = .048), but no difference in mortality. In critical illness, delayed enteral feeding appears to have little impact on either GE or the enterogastric feedback hormones. However, the association between delayed feeding and increased duration of ventilation and length of stay in the ICU supports the current recommendation that enteral nutrition should be commenced early.

Sleeve Fracture of the Superior Pole of the Patella with an Intra-Articular Dislocation

Patellar fractures in children are uncommon and represent 1% of all pediatric fractures1-3. Of all patellar fractures, less than 2% occur in the skeletally immature patient2. Intra-articular dislocation of the patella is also a rare occurrence. Sleeve fractures represent the most common type of patellar fracture in children2, with most reported cases involving sleeve fractures of the inferior patellar pole. To our knowledge, only two cases of sleeve fractures of the superior pole have been reported in the English-language literature4,5 and the association of a sleeve fracture of the superior patellar pole with an intra-articular dislocation of the patella has not been previously reported. Our patient and his family were informed that data concerning the case would be submitted for publication, and they consented. A fourteen-year-old boy presented to our institution after sustaining a direct blow to the suprapatellar area of the right knee. The injury occurred as a result of the knee striking a concrete block while the patient was swinging on a rope. Following the injury, the boy was unable to walk and could not move the right knee. Examination revealed bruising of the anterior aspect of the knee and an unusual shape of the patella. The patient could neither perform a straight leg raise nor flex the knee. Radiographs of the knee revealed an intra-articular dislocation of the patella (Figs. 1-A and 1-B). In the lateral projection (Fig. 1-B), the patella was seen to be lying in a transverse position, with the articular surface facing in a distal direction. Fig. 1-A Fig. 1-B Preoperative anteroposterior (Fig. 1-A) and lateral (Fig. 1-B) radiographs of the knee, showing the transverse orientation of the patella with the articular surface facing in a distal direction. With the patient under intravenous morphine sedation, the patella …

A randomized clinical trial of oral transmucosal fentanyl citrate versus intravenous morphine sulfate for initial control of pain in children with extremity injuries

Background Extremity injury is a common condition that requires pain management in an emergency department. In pediatric patients, the most frequently used method of pain control is intravenous (IV) morphine sulfate. Oral transmucosal fentanyl citrate (OTFC) is a potential alternative to morphine, which may obviate the need to place an IV before addressing pain. Objective To compare OTFC with IV morphine for sedation and analgesia during initial evaluation of children with deformity of an extremity and suspected fracture. Design/methods A randomized controlled trial of OTFC versus IV morphine in which 8- to 18-year-olds presenting to pediatric tertiary care emergency department with extremity deformity and suspected fracture were eligible. Only those with visual analog scale (VAS) (0 = no pain, 100 = worst pain imaginable) score equal to or greater than 50/100, and American Society of Anesthesia I or II qualified. Patients were excluded if history of loss of/altered level of consciousness, multiple traumatic injuries, or if patient had received prior medication for pain control. All patients enrolled were randomly assigned to receive either IV morphine (0.1 mg/kg) or OTFC (10-15 mug/kg). Patients rated pain intensity using VAS; scores were recorded before medicating and at 15-minute intervals after the medication was given. Adverse events such as emesis, pruritus, and respiratory depression were recorded. Results A total of 87 patients were enrolled in study (OTFC, 47; morphine, 40). There are no significant differences between the 2 groups when comparing sex, age, weight, and pretreatment VAS score (P > 0.05). Although the VAS scores were not significantly different before medicating the patient, an analysis of variance shows that there was a significant difference (P > 0.05) in VAS scores at 30 minutes. The differences persisted for every 15 minutes through the 75 minutes of monitoring. There was no statistically significant difference between the 2 groups when comparing the number of adverse events (P = 0.23). Conclusions The use of OTFC can provide improved pain control when compared with IV morphine. The pain reduction starts 30 minutes after initiation of medication, and the effect is seen as far as 75 minutes after the initiation of analgesic medication. The study size was too small to make any statements concerning adverse effects; thus, further studies with larger sample sizes are needed to determine the use of OTFC.

Can Electroencephalographic Analysis Be Used to Determine Sedation Levels in Critically Ill Patients?

Prolonged use of sedative drugs frequently leads to oversedation of intensive care patients. Clinical assessment scales are not reliable in deeply sedated patients. Parameters obtained from spectral and bispectral analysis of electroencephalogram (EEG) records have been combined to create an index (BIS) to monitor anesthesia depth. The role of such parameters in monitoring the depth of the sedation in intensive care unit (ICU) patients has yet to be determined. We designed the present prospective study to redefine and calculate available spectral and bispectral parameters from raw EEG records and estimate their clinical relevance for the diagnosis of under- or oversedation levels in ICU patients. Forty adult patients receiving continuous midazolam and morphine sedation were included. We obtained 167 clinical evaluations of sedation level using Ramsay and COMFORT scales along with an EEG record of 300 s. Six spectral parameters-relative power of 4 frequency bands (beta, alpha, Theta, and delta), 95th percentile of the power spectrum (SEF95), and 50th percentile of the power spectrum (SEF50) and four bispectral parameters, real triple product, bispectrum (Bispectrum), bicoherence, and ratio 10-were calculated. The relevance of each of these parameters and combinations in predicting too light (Ramsay 1 and 2) or deep (Ramsay 5 and 6) sedation levels was assessed. These calculations were performed before and after exclusion of the agitated patients, whose COMFORT 4 score was above 2. The most relevant parameters for predicting levels of deep sedation (Ramsay 5 and 6) were ratio 10 (area under the curve = 0.763; 95% confidence interval, 0.679-0.833) and SEF95 (area under the curve = 0.687; 95% confidence interval, 0.597-0.767). The most relevant parameters for predicting light levels of sedation (Ramsay 1 and 2) were also ratio 10 (area under the curve = 0.829; 95% confidence interval, 0.695-0.917) and SEF95 (area under the curve = 0.798; 95% confidence interval, 0.650-0.898). There is a modest improvement in relevance of their linear combination in predicting sedation level. Results were similar after exclusion of agitated patients. We conclude that various calculated EEG descriptive parameters exhibited large interindividual variability. There was a strong correlation between EEG spectral and bispectral parameters. Bispectral analysis slightly improves the predictive power of simple spectral analysis in distinguishing too light or deep sedation levels in ICU patients. Spectral edge frequency 95 and Ratio 10 are the most relevant electroencephalogram (EEG) indexes for monitoring the level of sedation in intensive care unit patients but calculated EEG values exhibited large interindividual variability. Bispectral analysis of EEG provides a slight improvement over simple spectral analysis.

Morphine Sedation in Ventilated Newborns: Who Are We Treating?

The use of sedation in ill, ventilated preterm infants is common,1 and its use in recent years seems to have increased in frequency.2 The reason that opiates have become more widely prescribed is the belief that infants adversely respond to painful stimuli associated with neonatal intensive care and that this may have adverse long-term consequences. In addition, evidence has been presented to indicate that sedation may reduce both respiratory and neurologic complications; unfortunately, none of these propositions have been reported consistently to be correct. Is there sufficient evidence that we are benefiting infants, or rather reassuring staff that infants are not suffering pain during intensive care? In this issue of Pediatrics , Bhandari and colleagues3 present data on the largest randomized, control trial (NEOPAIN) performed to date on the short-term respiratory effects of morphine infusion in 898 ventilated very preterm infants. They report that for all but the most immature infants, the duration of time on the ventilator was prolonged in the morphine-treated group compared with controls. The overall difference was 1 day longer of positive-pressure ventilation. The study design allowed open-label morphine (additional analgesia [AA]) to be given as mandated by the physician caring for the infant. When all the data were analyzed in a logistic-regression model including perinatal complications that might explain lung damage, AA was independently associated with increased air leaks and prolonged need for nasal continuous positive airway pressure and oxygen therapy, … Address correspondence to Malcolm Levene, MD, FRCPCH, Department of Paediatrics and Child Health, Leeds General Infirmary, D Floor, Clarendon Wing, Leeds LS2 9NS, United Kingdom. E-mail: m.i.levene{at}leeds.ac.uk