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Klinische Padiatrie Jul 2021Analgosedation is often used for endotracheal intubation in neonates, but no consensus exists on the optimal pre-procedural medication.
BACKGROUND
Analgosedation is often used for endotracheal intubation in neonates, but no consensus exists on the optimal pre-procedural medication.
AIMS
To compare the time to intubation and vital signs during and after intubation in 2 NICUs using different premedication protocols.
METHODS
Prospective observational study in 2 tertiary NICUs, comparing fentanyl and optional vecuronium for elective neonatal endotracheal intubation (NICU-1) with atropine, morphine, midazolam and optional pancuronium (NICU-2). Primary endpoints were: time to intubate and number of intubation attempts; secondary endpoints were: deviations of heart rate, oxygen saturation and blood pressure from baseline until 20 min post intubation.
RESULTS
45 and 30 intubations were analyzed in NICU-1 and NICU-2. Time to intubation was longer in NICU-1 (7 min) than in NICU-2 (4 min; p=0.029), but the mean number of intubation attempts did not differ significantly. Bradycardias (34 vs. 1, p<0.001) and hypoxemias (136 vs. 48, p<0.001) were more frequent in NICU-1, and tachycardias (59 vs. 72, p<0.001) more frequent in NICU-2. Mean arterial blood pressure (MAP) increased in NICU-1 (+6.18 mmHg) and decreased in NICU-2 (-5.83 mmHg), whereas mean heart rates (HR) decreased in NICU-1 (-19.29 bpm) and increased in NICU-2 (+15.93 bpm). MAP and HR returned to baseline 6-10 min after intubation in NICU-1 and after 11-15 min and 16-20 min in NICU-2, respectively.
CONCLUSIONS
The two protocols yielded significant differences in the time to intubation and in the extent and duration of physiologic changes during and post-intubation. Short acting drugs should be preferred and vital signs should be closely monitored at least 20 min post intubation. More studies are required to identify analgosedation protocols that minimize potentially harmful events during endotracheal intubation.
Topics: Humans; Infant, Newborn; Intubation, Intratracheal; Midazolam; Morphine; Observational Studies as Topic; Premedication; Vital Signs
PubMed: 33465783
DOI: 10.1055/a-1330-8538 -
Anesthesiology Feb 2023Cerebral Function and Muscle Afferent Activity Following Intravenous Succinylcholine in Dogs Anesthetized with Halothane: The Effects of Pretreatment with a...
Cerebral Function and Muscle Afferent Activity Following Intravenous Succinylcholine in Dogs Anesthetized with Halothane: The Effects of Pretreatment with a Defasciculating Dose of Pancuronium. By WL Lanier, PA Iaizzo, and JH Milde. Anesthesiology 1989; 71:87-95. Reprinted with permission. By the mid-1980s, it was widely assumed that if the depolarizing muscle relaxant, succinylcholine, given IV, produced increases in intracranial pressure, it did so because fasciculations produced increases in intrathoracic and central venous pressures that were transferred to the brain; however, there was no direct evidence that this was true. In contrast, we explored the possibility that the succinylcholine effect on the brain was explained by the afferentation theory of cerebral arousal, which predicts that agents or maneuvers that stimulate muscle stretch receptors will tend to stimulate the brain. Our research in tracheally intubated, lightly anesthetized dogs discovered that IV succinylcholine (which does not cross the blood-brain barrier) produced a doubling of cerebral blood flow that lasted for 30 min and corresponded to activation of the electroencephalogram and increases in intracranial pressure. Later, in our Classic Paper, we were able to assess simultaneously cerebral physiology and afferent nerve traffic emanating from muscle stretch receptors (primarily muscle spindles). We affirmed that the cerebral arousal response to succinylcholine was indeed driven by muscle afferent traffic and was independent of fasciculations or increases in intrathoracic or central venous pressures. Later research in complementary models demonstrated that endogenous movement (e.g., coughing, hiccups) produced a cerebral response very similar to IV succinylcholine, apparently as a result of the same muscle afferent mechanisms, independent of intrathoracic and central venous pressures. Thus, the importance of afferentation theory as a driver of the cerebral state of arousal and cerebral physiology during anesthesia was affirmed.
Topics: Animals; Dogs; Succinylcholine; Fasciculation; Anesthesia; Halothane; Muscles
PubMed: 36629464
DOI: 10.1097/ALN.0000000000004437 -
European Journal of Anaesthesiology Jul 2019Nondepolarising muscle relaxants (NDMRs) provide optimal conditions for tracheal intubation and improve surgical conditions. Several clinical conditions, diseases and...
BACKGROUND
Nondepolarising muscle relaxants (NDMRs) provide optimal conditions for tracheal intubation and improve surgical conditions. Several clinical conditions, diseases and pharmacological interactions have been suggested to cause resistance towards NDMRs that may translate into difficult intubation or inadequate operating conditions during surgery.
OBJECTIVE
The aim of this study was to evaluate the current evidence of patient groups with resistance towards NDMRs. A prolonged onset time was defined as a difference that exceeded 25% compared with controls.
DESIGN
A systematic review of randomised controlled trials and cohort studies.
DATA SOURCES
A comprehensive search was performed in 2016 in PubMed and EMBASE.
ELIGIBILITY CRITERIA
Patients with conditions or diseases, or patients taking medication, which lead to resistance towards current NDMRs (rocuronium, vecuronium, cisatracurium, atracurium, mivacurium and pancuronium). Included outcomes were onset time defined as the time between administration of NDMR to maximal (90, 95 or 100%) depression of baseline twitch height of the first twitch in a train-of-four.
RESULTS
Twenty-five studies were included. Strong evidence supports a prolonged onset time of rocuronium in patients with thermal injury and Duchenne muscular dystrophy. Moderate evidence supports a prolonged onset time of NDMRs during hypothermia and in patients with infection, oculopharyngeal muscular dystrophy, liver cirrhosis treated with ulinastatin, when remifentanil is administered prior to administration of an NDMR, in fasting patients being rehydrated intravenously prior to administration of NDMR, in children with end-stage renal failure and in patients with atrial or ventricular septal defects.
CONCLUSION
A prolonged onset time should be suspected in patients with thermal injury and Duchenne's muscular dystrophy. Further, evidence supports a prolonged onset time in patients with infection, oculopharyngeal muscular dystrophy, congenital heart defects, kidney failure, liver cirrhosis treated with ulinastatin along with remifentanil or intravenous fluids administered prior to NDMR.
Topics: Drug Resistance; Humans; Neuromuscular Blockade; Neuromuscular Nondepolarizing Agents; Randomized Controlled Trials as Topic; Risk Factors; Time Factors
PubMed: 30950905
DOI: 10.1097/EJA.0000000000000991 -
Canadian Journal of Anaesthesia =... Mar 2022Malignant hyperthermia (MH) is a hypermetabolic disorder that can occur in genetically susceptible individuals exposed to halogenated anesthetics and succinylcholine....
PURPOSE
Malignant hyperthermia (MH) is a hypermetabolic disorder that can occur in genetically susceptible individuals exposed to halogenated anesthetics and succinylcholine. Spinal cord injury (SCI) above the sixth thoracic vertebra is associated with dysfunction of the sympathetic/parasympathetic nervous pathways, including thermoregulatory dysfunction, presenting as hypothermia in cold environments because of vasodilation and heat loss. This effect could mitigate or obscure an MH episode. Here, we describe development of a fatal MH crisis in a patient with SCI.
CLINICAL FEATURES
A 27-yr-old male patient with an SCI after fracture of the sixth cervical vertebra was admitted for spinal arthrodesis. Anesthetic medications included remifentanil, propofol, succinylcholine, rocuronium, and isoflurane. After the start of the surgery, muscular contractures resembling myoclonus were noted, which resolved with pancuronium administration. Four hours after the start of anesthesia, the patient presented with hyperthermia, hypercarbia, hypotension, muscle rigidity, arrhythmia, and cardiogenic shock, with metabolic/respiratory acidosis. Malignant hyperthermia was suspected and the treatment was started, but he developed cardiopulmonary arrest and died an hour and a half after the first cardiac arrest. Both parents were investigated and were found to have normal creatine kinase levels and positive in vitro contracture tests. His mother carried a variant in the ryanodine receptor type 1 (RYR1) gene (c.14918C>T), which is associated with MH.
CONCLUSION
Spinal cord injury-induced thermoregulatory dysfunction may obscure the early diagnosis of MH and lead to fatal outcome.
Topics: Adult; Anesthetics; Humans; Isoflurane; Male; Malignant Hyperthermia; Ryanodine Receptor Calcium Release Channel; Spinal Cord Injuries; Succinylcholine
PubMed: 34904211
DOI: 10.1007/s12630-021-02170-4 -
International Journal of Molecular... Sep 2021Paediatric acute myeloid leukaemia (AML) is a heterogeneous disease characterised by the malignant transformation of myeloid precursor cells with impaired...
Paediatric acute myeloid leukaemia (AML) is a heterogeneous disease characterised by the malignant transformation of myeloid precursor cells with impaired differentiation. Standard therapy for paediatric AML has remained largely unchanged for over four decades and, combined with inadequate understanding of the biology of paediatric AML, has limited the progress of targeted therapies in this cohort. In recent years, the search for novel targets for the treatment of paediatric AML has accelerated in parallel with advanced genomic technologies which explore the mutational and transcriptional landscape of this disease. Exploiting the large combinatorial space of existing drugs provides an untapped resource for the identification of potential combination therapies for the treatment of paediatric AML. We have previously designed a multiplex screening strategy known as Multiplex Screening for Interacting Compounds in AML (MuSICAL); using an algorithm designed in-house, we screened all pairings of 384 FDA-approved compounds in less than 4000 wells by pooling drugs into 10 compounds per well. This approach maximised the probability of identifying new compound combinations with therapeutic potential while minimising cost, replication and redundancy. This screening strategy identified the triple combination of glimepiride, a sulfonylurea; pancuronium dibromide, a neuromuscular blocking agent; and vinblastine sulfate, a vinca alkaloid, as a potential therapy for paediatric AML. We envision that this approach can be used for a variety of disease-relevant screens allowing the efficient repurposing of drugs that can be rapidly moved into the clinic.
Topics: Antineoplastic Agents; Blotting, Western; Cell Line; Cell Line, Tumor; Cell Survival; Drug Repositioning; Flow Cytometry; Humans; Leukemia, Myeloid, Acute; Mutation
PubMed: 34576326
DOI: 10.3390/ijms221810163 -
The Journal of Pediatrics Jan 2022To provide up-to-date medication prescribing patterns in US neonatal intensive care units (NICUs) and to examine trends in prescribing patterns over time.
OBJECTIVE
To provide up-to-date medication prescribing patterns in US neonatal intensive care units (NICUs) and to examine trends in prescribing patterns over time.
STUDY DESIGN
We performed a cohort study of 799 016 infants treated in NICUs managed by the Pediatrix Medical Group from 2010 to 2018. We used 3 different methods to report counts of medication: exposure, courses, and days of use. We defined the change in frequency of medication administration by absolute change and relative change. We examined the Food and Drug Administration (FDA) package insert for each medication to determine whether a medication was labeled for use in infants and used PubMed to search for pharmacokinetics (PK) studies.
RESULTS
The most frequently prescribed medications included ampicillin, gentamicin, caffeine citrate, poractant alfa, morphine, vancomycin, furosemide, fentanyl, midazolam, and acetaminophen. Of the top 50 medications used in infants with extremely low birth weight, only 20 (40%) are FDA-labeled for use in infants; of the 30 that are not labeled for use in infants, 13 (43%) had at least 2 published PK studies. The medications with the greatest relative increase in use from 2010 to 2018 included dexmedetomidine, clonidine, rocuronium, levetiracetam, atropine, and diazoxide. The medications with the greatest relative decrease in use included tromethamine acetate, pancuronium, chloral hydrate, imipenem + cilastatin, and amikacin.
CONCLUSION
Trends of medication use in the NICU change substantially over time. It is imperative to identify changes in medication use in the NICU to better inform further prospective studies.
Topics: Cohort Studies; Databases, Factual; Drug Utilization; Humans; Infant, Newborn; Intensive Care Units, Neonatal; Pharmaceutical Preparations; United States
PubMed: 34481808
DOI: 10.1016/j.jpeds.2021.08.075 -
European Journal of Pharmaceutical... Aug 2023During the early months of the COVID-19 pandemic, the international medical product supply chain was tight, causing breaks in the availability of neuromuscular blocking...
Predictive stability, novel HPLC-MS analysis and semi-automatic compounding process for the emergency implementation of a production line of pancuronium in injectable solution.
During the early months of the COVID-19 pandemic, the international medical product supply chain was tight, causing breaks in the availability of neuromuscular blocking agents essential for the treatment of patients in intensive care units. The present study describes the pharmaceutical development of an injectable 2 mg/mL solution of pancuronium bromide (PC) in a very short lapse of time. The sterile solution was compounded into a good manufacturing practice grade A clean room, filtered (0.2 µm) and filled into 10 mL type I glass, manually sealed with bromobutyl rubber stoppers. A novel HPLC-MS stability indicating method for pancuronium quantification and its degradation product was developed and validated. This fast, sensitive and straightforward method was used to study the stability of the formulation using a semi-predictive method, enabling a very fast attribution of a temporary shelf-life, which was confirmed by a classic prospective stability study. The production line and the analytical tools set-up were performed in six weeks and the semi-predictive stability study was conducted in 90 days, allowing us to predict a shelf life, which was successfully confirmed by prospective study. In conclusion, using innovative methods, we were able to rapidly overcome the shortage of a critical drug.
Topics: Humans; Chromatography, High Pressure Liquid; Pancuronium; Prospective Studies; Pandemics; COVID-19; Drug Stability; Drug Compounding
PubMed: 37169099
DOI: 10.1016/j.ejps.2023.106464 -
Chemical Science Aug 2022Supramolecular sequestration and reversal of neuromuscular block (NMB) have great clinical applications. Water-soluble flexible organic frameworks (FOFs) cross-linked by...
Supramolecular sequestration and reversal of neuromuscular block (NMB) have great clinical applications. Water-soluble flexible organic frameworks (FOFs) cross-linked by disulfide bonds are designed and prepared. Different linker lengths are introduced to FOFs to give them varied pore sizes. FOFs are anionic nanoscale polymers and capable of encapsulating cationic neuromuscular blocking agents (NMBAs), including rocuronium (Roc), vecuronium (Vec), pancuronium (Panc) and cisatracurium (Cis). A host-guest study confirms that FOFs bind NMBAs in water. The multivalency interaction between FOFs and NMBAs is able to sequester NMBAs, and prevent them from escaping. These FOFs are non-toxic and biocompatible. Animal studies show that FOFs are effective for the reversal of NMB induced by Roc, Vec and Cis, which shorten the time to a train-of-four ratio of 0.9 by 2.6, 3.8 and 5.7-fold compared to a placebo, respectively.
PubMed: 36093029
DOI: 10.1039/d2sc02456j -
Brain Communications 2020Mechanisms of motor deficits (e.g. hemiparesis and hemiplegia) secondary to stroke and traumatic brain injury remain poorly understood. In early animal studies, a...
Mechanisms of motor deficits (e.g. hemiparesis and hemiplegia) secondary to stroke and traumatic brain injury remain poorly understood. In early animal studies, a unilateral lesion to the cerebellum produced postural asymmetry with ipsilateral hindlimb flexion that was retained after complete spinal cord transection. Here we demonstrate that hindlimb postural asymmetry in rats is induced by a unilateral injury of the hindlimb sensorimotor cortex, and characterize this phenomenon as a model of spinal neuroplasticity underlying asymmetric motor deficits. After cortical lesion, the asymmetry was developed due to the contralesional hindlimb flexion and persisted after decerebration and complete spinal cord transection. The asymmetry induced by the left-side brain injury was eliminated by bilateral lumbar dorsal rhizotomy, but surprisingly, the asymmetry after the right-side brain lesion was resistant to deafferentation. Pancuronium, a curare-mimetic muscle relaxant, abolished the asymmetry after the right-side lesion suggesting its dependence on the efferent drive. The contra- and ipsilesional hindlimbs displayed different musculo-articular resistance to stretch after the left but not right-side injury. The nociceptive withdrawal reflexes evoked by electrical stimulation and recorded with EMG technique were different between the left and right hindlimbs in the spinalized decerebrate rats. On this asymmetric background, a brain injury resulted in greater reflex activation on the contra- versus ipsilesional side; the difference between the limbs was higher after the right-side brain lesion. The unilateral brain injury modified expression of neuroplasticity genes analysed as readout of plastic changes, as well as robustly impaired coordination of their expression within and between the ipsi- and contralesional halves of lumbar spinal cord; the effects were more pronounced after the left side compared to the right-side injury. Our data suggest that changes in the hindlimb posture, resistance to stretch and nociceptive withdrawal reflexes are encoded by neuroplastic processes in lumbar spinal circuits induced by a unilateral brain injury. Two mechanisms, one dependent on and one independent of afferent input may mediate asymmetric hindlimb motor responses. The latter, deafferentation resistant mechanism may be based on sustained muscle contractions which often occur in patients with central lesions and which are not evoked by afferent stimulation. The unusual feature of these mechanisms is their lateralization in the spinal cord.
PubMed: 32954305
DOI: 10.1093/braincomms/fcaa055 -
Anaesthesia Sep 2022Residual neuromuscular blockade is associated with significant morbidity. It has been widely studied in anaesthesia; however, the incidence of residual neuromuscular... (Observational Study)
Observational Study
Residual neuromuscular blockade is associated with significant morbidity. It has been widely studied in anaesthesia; however, the incidence of residual neuromuscular blockade in patients managed in the ICU is unknown. We conducted a prospective observational study in a tertiary ICU to determine the incidence of residual neuromuscular blockade using quantitative accelerographic monitoring. We tested for residual neuromuscular blockade (defined as a train-of-four ratio < 0.9) before cessation of sedation in anticipation of tracheal extubation. We also surveyed 16 other ICUs in New Zealand to determine their use of neuromuscular monitoring. A total of 191 patients were included in the final analysis. The incidence (95%CI) of residual neuromuscular blockade was 43% (36-50%), with a similar incidence observed in non-postoperative and postoperative patients. There was a lower risk of residual neuromuscular blockade with atracurium than rocuronium (risk ratio (95%CI) of 0.39 (0.12-0.78)) and a higher risk with pancuronium than rocuronium (1.59 (1.06-2.49)). Our survey shows that, in New Zealand ICUs, monitoring of neuromuscular function is rarely carried out before tracheal extubation. When neuromuscular monitoring is undertaken, it is based on individual clinician suspicion and performed using qualitative measurements. No ICU reported using a quantitative monitor or a clinical guideline. The results demonstrate a high incidence of residual neuromuscular blockade in our ICU patients and identify the type of neuromuscular blocking drug as a possible risk factor. Monitoring neuromuscular function before tracheal extubation is not currently the standard of care in New Zealand ICUs. These data suggest that residual neuromuscular blockade may be an under-recognised problem in ICU practice.
Topics: Delayed Emergence from Anesthesia; Humans; Neuromuscular Blockade; Neuromuscular Monitoring; Neuromuscular Nondepolarizing Agents; Rocuronium
PubMed: 35837762
DOI: 10.1111/anae.15789