Lars I. Eriksson

Functional assessment of the pharynx at rest and during swallowing in partially paralyzed humans: simultaneous videomanometry and mechanomyography of awake human volunteers

Background: Functional characteristics of the pharynx and upper esophagus, including aspiration episodes, were investigated in 14 awake volunteers during various levels of partial neuromuscular block. Pharyngeal function was evaluated using videoradiography and computerized pharyngeal manometry during contrast bolus swallowing. Methods: Measurements of pharyngeal constrictor muscle function (contraction amplitude, duration, and slope), upper esophageal sphincter muscle resting tone, muscle coordination, bolus transit time, and aspiration under fluoroscopic control (laryngeal or tracheal penetration) were made before (control measurements) and during a vecuronium‐induced partial neuromuscular paralysis, at fixed intervals of mechanical adductor pollicis muscle train‐of‐four (TOF) fade; that is, at TOF ratios of 0.60, 0.70, 0.80, and after recovery to a TOF ratio > 0.90. Results: Six volunteers aspirated (laryngeal penetration) at a TOF ratio < 0.90. None of them aspirated at a TOF ratio > 0.90 or during control recording. Pharyngeal constrictor muscle function was not affected at any level of paralysis. The upper esophageal sphincter resting tone was significantly reduced at TOF ratios of 0.60, 0.70, and 0.80 (P < 0.05). This was associated with reduced muscle coordination and shortened bolus transit time at a TOF ratio of 0.60. Conclusions: Vecuronium‐induced partial paralysis cause pharyngeal dysfunction and increased risk for aspiration at mechanical adductor pollicis TOF ratios < 0.90. Pharyngeal function is not normalized until an adductor pollicis TOF ratio of > 0.90 is reached. The upper esophageal sphincter muscle is more sensitive to vecuronium than is the pharyngeal constrictor muscle.

The incidence and mechanisms of pharyngeal and upper esophageal dysfunction in partially paralyzed humans: pharyngeal videoradiography and simultaneous manometry after atracurium.

Background: Residual neuromuscular block caused by vecuronium alters pharyngeal function and impairs airway protection. The primary objectives of this investigation were to radiographically evaluate the swallowing act and to record the incidence of and the mechanism behind pharyngeal dysfunction during partial neuromuscular block. The secondary objective was to evaluate the effect of atracurium on pharyngeal function. Methods: Twenty healthy volunteers were studied while awake during liquid-contrast bolus swallowing. The incidence of pharyngeal dysfunction was studied by fluoroscopy. The initiation of the swallowing process, the pharyngeal coordination, and the bolus transit time were evaluated. Simultaneous manometry was used to document pressure changes at the tongue base, the pharyngeal constrictor muscles, and the upper esophageal sphincter. After control recordings, an intravenous infusion of atracurium was administered to obtain train-of-four ratios (T4/T1) of 0.60, 0.70, and 0.80, followed by recovery to a train-of-four ratio of more than 0.90. Results: The incidence of pharyngeal dysfunction was 6% during the control recordings and increased (P < 0.05) to 28%, 17%, and 20% at train-of-four ratios 0.60, 0.70, and 0.80, respectively. After recovery to a train-of-four ratio of more than 0.90, the incidence was 13%. Pharyngeal dysfunction occurred in 74 of 444 swallows, the majority (80%) resulting in laryngeal penetration. The initiation of the swallowing reflex was impaired during partial paralysis (P = 0.0081). The pharyngeal coordination was impaired at train-of-four ratios of 0.60 and 0.70 (P < 0.01). A marked reduction in the upper esophageal sphincter resting tone was found, as well as a reduced contraction force in the pharyngeal constrictor muscles. The bolus transit time did not change significantly. Conclusion: Partial neuromuscular paralysis caused by atracurium is associated with a four- to fivefold increase in the incidence of misdirected swallowing. The mechanism behind the pharyngeal dysfunction is a delayed initiation of the swallowing reflex, impaired pharyngeal muscle function, and impaired coordination. The majority of misdirected swallows resulted in penetration of bolus to the larynx.

Resolving postoperative neuroinflammation and cognitive decline

Cognitive decline accompanies acute illness and surgery, especially in the elderly. Surgery engages the innate immune system that launches a systemic inflammatory response that, if unchecked, can cause multiple organ dysfunction. We sought to understand the mechanisms whereby the brain is targeted by the inflammatory response and how this can be resolved.

Acute quadriplegia and loss of muscle myosin in patients treated with nondepolarizing neuromuscular blocking agents and corticosteroids : mechanisms at the cellular and molecular levels

Objective: Long‐term treatment with nondepolarizing neuromuscular blocking agents and corticosteroids in the intensive care unit is not benign, and an increasing number of patients with acute quadriplegic myopathy have been reported with increased use of these drugs. The purpose of this study was to investigate the mechanisms underlying acute quadriplegic myopathy. Design: Percutaneous muscle biopsy samples were obtained, and electrophysiologic examinations were performed during the acute phase and during recovery in patients with acute quadriplegic myopathy. Regulation of muscle contraction and myofibrillar protein synthesis was studied using cell physiologic techniques, ultrasensitive electrophoresis, in situ hybridization, and histopathologic techniques. Setting: All patients were seen in the intensive care unit of different university hospitals. Patients: All patients were critically ill with sepsis. They had been given massive doses of corticosteroids in combination with variable doses of neuromuscular blocking agents. All patients developed paralysis of spinal nerve‐innervated muscles. On the other hand, cranial nerve‐innervated muscle and sensory and cognitive functions were well maintained after discontinuation of treatment with neuromuscular blocking agents. Intervention: Muscle biopsy samples were obtained and electrophysiologic examinations were performed in all patients. Measurements and Main Results: The major observations in patients with acute quadriplegic myopathy were, as follows: a) a general decrease in myofibrillar protein content; b) specific but highly variable partial or complete loss of myosin and myosin‐associated proteins; c) very low thick‐filament/thin‐filament protein ratios; d) absence of myosin messenger RNA; and e) a dramatically impaired muscle cell force‐generating capacity in the acute phase of acute quadriplegic myopathy. During clinical improvement, normal expression of myosin messenger RNAs, reexpression of thick‐filament proteins, and increased specific tension were observed. Conclusions: Acute quadriplegic myopathy is associated with a specific decrease in thick‐filament proteins related to an altered transcription rate. Although the decreased content of thick‐filament proteins is important for prolonged muscle weakness, it is not the primary cause of muscle paralysis in the acute stage, during which impaired muscle membrane excitability probably plays a more significant role. Several factors contribute to this condition, but the action of corticosteroids seems to be the predominant one, along with potentiation by neuromuscular blocking agents, immobilization, and probably also concurrent sepsis.

Pre‐operative fasting guidelines: an update

Liberal pre‐operative fasting routines have been implemented in most countries. In general, clear fluids are allowed up to 2 h before anaesthesia, and light meals up to 6 h. The same recommendations apply for children and pregnant women not in labour. In children <6 months, most recommendations now allow breast‐ or formula milk feeding up to 4 h before anaesthesia. Recently, the concept of pre‐operative oral nutrition using a special carbohydrate‐rich beverage has also gained support and been shown not to increase gastric fluid volume or acidity. Based on the available literature, our Task Force has produced new consensus‐based Scandinavian guidelines for pre‐operative fasting. What is still not clear is to what extent the new liberal fasting routines should apply to patients with functional dyspepsia or systematic diseases such as diabetes mellitus. Other still controversial areas include the need for and effect of fasting in emergency patients, women in labour and in association with procedures done under ‘deep sedation’. We think more research on the effect of various fasting regimes in subpopulations of patients is needed before we can move one step further towards completely evidence‐based pre‐operative fasting guidelines.

Evidence-based practice and neuromuscular monitoring: it's time for routine quantitative assessment.

OVER the last years, a growing body of information has accumulated in the anesthesia literature about the advantages and pitfalls of various techniques used for quantitatively monitoring neuromuscular function in routine anesthetic practice and the associated incidence (and consequences) of residual neuromuscular block in the postoperative period. Many methods are available, ranging from quantitative strain–gauge techniques, electromyography, acceleromyography, phonomyography, etc. However, quantitative techniques are not widely used, with most anesthesiologists relying on visual or tactile assessment of the train-of-four (TOF) ratio, or, in many cases, no neuromuscular monitoring at all. One argument for such qualitative approaches to monitoring is that with modern short and intermediate acting relaxants, residual paralysis is not a clinical problem or, even if patients are not completely reversed by the end of the case, the block will dissipate in a few minutes. Another approach is “reverse everyone,” which is viewed by some as uniformly easy, safe, and effective for patients given these agents. There is now increasing evidence that this relaxed attitude to neuromuscular monitoring is unwise. The study by Debaene et al., published in this issue of ANESTHESIOLOGY, has a clear message to all of us. The authors examined the incidence and magnitude of a neuromuscular block on arrival in the PACU in a large group of relatively unselected patients who had received a single dose of intermediate-duration relaxant for intubation (rocuronium, vecuronium, or atracurium). Patients received no other relaxant during their surgery and did not receive reversal agents at any time. The message is that, while it may be presumed that the attending anesthesiologists felt that adequate neuromuscular function was present at the time of transfer, 45% of the patients arrived in the recovery room with a residual neuromuscular block, defined as an adductor pollicis TOF ratio of less than 0.90! Sixteen percent had a TOF ratio of less than 0.7. Interestingly, in sufficiently cooperative patients, even clinical tests were frequently abnormal; 15% of tested patients failed a test of head lift. Even in patients tested more than 2 h after drug administration, the incidences of residual paralysis were 10 and 37% (based on a TOF ratio of less than 0.7 or less than 0.9, respectively). The specific relaxant used did not influence these incidences. The study was not a rigorous study of drug kinetics or twitch depression and recovery. Instead, the authors examined something close to routine clinical practice; that is, the anesthesiologist was free to select the neuromuscular blocking drug, the dose, and whether to use or not use neuromuscular monitoring. There are clearly experimental problems with this approach, and it is unfortunate that the authors did not provide further information about the actual anesthetic practice (in particular whether or not some form of monitoring was used). This limits the external validity of the study. Nevertheless, the results clearly demonstrate that a disturbingly high fraction of patients did not have adequate neuromuscular function on arrival in the recovery room. Recently, several studies focusing on this kind of broad, unselected patient population have been published. They all found an alarmingly high incidence of residual paralysis in the recovery room despite the use of intermediate acting neuromuscular blocking agents (vecuronium, rocuronium, atracurium, and cisatracurium). There are several possible explanations for this unexpectedly high incidence. One reason might be the change in definition of clinically significant residual paralysis from a TOF ratio of 0.70 to 0.90. However, since clinical measures are also commonly abnormal, this cannot be a complete explanation. Thus, it is clear that the widespread belief that intermediate-acting muscle relaxants have a very low tendency to cause residual paralysis (and therefore, that it is not necessary to monitor or even to reverse the neuromuscular block) is very wrong. Combining the results of the current study with the results from several similar investigations, there is now sufficient information to support a general change in the attitude towards monitoring and reversal of a neuromuscular block in routine anesthetic practice. Though anesthesiologists probably have a relatively low threshold for carrying new monitoring equipment into the operating room (e.g., BIS, AEP, ST-analysis, endtidal anesthetic gas concentrations, etc.), few techniques have been documented to affect patient outcome. In this This Editorial View accompanies the following article: Debaene B, Plaud B, Dilly M.-P., Donati F. Residual paralysis in the PACU after a single intubating dose of nondepolarizing muscle relaxant with an intermediate duration of action. ANESTHESIOLOGY 2003; 98:1042–8.

Effect of a vecuronium-induced partial neuromuscular block on hypoxic ventilatory response.

BackgroundA previous study has demonstrated a decrease in the hypoxic ventilatory response in volunteers partially paralyzed with vecuronium. However, in this study, hypocapnia was allowed to occur. Because hypocapnia counteracts the ventilatory response to hypoxia during partial vecuronium-induced neuromuscular block and isocapnia, the hypoxic ventilatory response (HVR) was tested in 10 awake volunteers. MethodsTo avoid hypocapnia, the resting hyperoxic control end-tidal PCO2 was increased to 43.3 ± 2.4 mmHg, raising inspiratory minute ventilation (&OV0312;1) to 140 ml·kg-1·min-1·Hypoxic ventilatory response (Δ&OV0312;1 /ΔSpO2, L·min-1·%-1) was measured during a 5-min isocapnic step reduction to a mean arterial hemoglobin oxygen saturation (SpO2) of 84.8 ± 1.4%. Immediately thereafter, hypercapnic ventilatory response (HCVR; δ&OV0312;1/ΔPetCO2, L·min-1·mmHg-1) was determined at the end of a 6-min step increase of PetCO2 to 50.5 ± 2.7 mmHg. During a subsequent 30–40-min pause, an intravenous infusion of vecuronium was adjusted to reduce the adductor pollicis train-of-four ratio to 0.70, as monitored using mechanomyography. Ventilatory parameters, HVR and HCVR, were then re-determined. ResultsResting &OV0312;1, PetCO2, and SpO2 were unchanged by drug infusion. Hypoxic ventilatory response decreased from control (a) of 0.97 ± 0.43 to 0.74 ± 0.41 L·min-1·%-1 (P < 0.02) during drug infusion (b), while HCVR was unchanged (a = 1.91 ± 0.82, b = 1.62 ± 0.46 L·min-1·mmHg-1; NS). To correct HVR for possible vecuronium-induced respiratory muscle weakness or otherwise altered central nervous system reactivity, the drug/control ratio (HVRb/a) was divided by the associated HCVRb/a ratio. This HVR index, FHVR was 0.84 ± 0.12 (P < 0.01). ConclusionsWe conclude that a vecuronium-induced partial neuromuscular block impairs HVR more than it does HCVR In humans, suggesting an effect of vecuronium on carotid body hypoxic chemosensitivity.

Opioid Action on Respiratory Neuron Activity of the Isolated Respiratory Network in Newborn Rats

BackgroundUnderlying mechanisms behind opioid-induced respiratory depression are not fully understood. The authors investigated changes in burst rate, intraburst firing frequency, membrane properties, as well as presynaptic and postsynaptic events of respiratory neurons in the isolated brainstem after administration of opioid receptor agonists. MethodsNewborn rat brainstem–spinal cord preparations were used and superfused with &mgr;-, &kgr;-, and &dgr;-opioid receptor agonists. Whole cell recordings were performed from three major classes of respiratory neurons (inspiratory, preinspiratory, and expiratory). ResultsMu- and &kgr;-opioid receptor agonists reduced the spontaneous burst activity of inspiratory neurons and the C4 nerve activity. Forty-two percent of the inspiratory neurons were hyperpolarized and decreased in membrane resistance during opioid-induced respiratory depression. Furthermore, under synaptic block by tetrodotoxin perfusion, similar changes of inspiratory neuronal membrane properties occurred after application of &mgr;- and &kgr;-opioid receptor agonists. In contrast, resting membrane potential and membrane resistance of preinspiratory and majority of expiratory neurons were unchanged by opioid receptor agonists, even during tetrodotoxin perfusion. Simultaneous recordings of inspiratory and preinspiratory neuronal activities confirmed the selective inhibition of inspiratory neurons caused by &mgr;- and &kgr;-opioid receptor agonists. Application of opioids reduced the slope of rising of excitatory postsynaptic potentials evoked by contralateral medulla stimulation, resulting in a prolongation of the latency of successive first action potential responses. ConclusionsMu- and &kgr;-opioid receptor agonists caused reduction of final motor outputs by mainly inhibiting medullary inspiratory neuron network. This inhibition of inspiratory neurons seems to be a result of both a presynaptic and postsynaptic inhibition. The central respiratory rhythm as reflected by the preinspiratory neuron burst rate was essentially unaltered by the agonists.

Perioperative Cognitive Decline in the Aging Population

Elderly patients who have an acute illness or who undergo surgery often experience cognitive decline. The pathophysiologic mechanisms that cause neurodegeneration resulting in cognitive decline, including protein deposition and neuroinflammation, also play a role in animal models of surgery-induced cognitive decline. With the aging of the population, surgical candidates of advanced age with underlying neurodegeneration are encountered more often, raising concerns that, in patients with this combination, cognitive function will precipitously decline postoperatively. This special article is based on a symposium that the University of California, San Francisco, convened to explore the contributions of surgery and anesthesia to the development of cognitive decline in the aged patient. A road map to further elucidate the mechanisms, diagnosis, risk factors, mitigation, and treatment of postoperative cognitive decline in the elderly is provided.

Pharyngeal function and airway protection during subhypnotic concentrations of propofol, isoflurane, and sevoflurane: volunteers examined by pharyngeal videoradiography and simultaneous manometry

Background Anesthetic agents alter pharyngeal function with risk of impaired airway protection and aspiration. This study was performed to evaluate pharyngeal function during subhypnotic concentrations of propofol, isoflurane, and sevoflurane and to compare the drugs for possible differences in this respect. Methods Forty-five healthy volunteers were randomized to receive propofol, isoflurane, or sevoflurane. During series of liquid contrast bolus swallowing, fluoroscopy and simultaneous solid state videomanometry was used to study the incidence of pharyngeal dysfunction, the initiation of swallowing, and the bolus transit time. Pressure changes were recorded at the back of the tongue, the pharyngeal constrictor muscles, and the upper esophageal sphincter. After control recordings, the anesthetic was delivered, and measurements were made at 0.50 and 0.25 predicted blood propotol concentration (Cp50asleep) for propofol and 0.50 and 0.25 minimum alveolar concentration (MAC)awake for the inhalational agents. Final recordings were made 20 min after the end of anesthetic delivery. Results All anesthetics caused an increased incidence of pharyngeal dysfunction with laryngeal bolus penetration. Propofol increased the incidence from 8 to 58%, isoflurane from 4 to 36%, and sevoflurane from 6 to 35%. Propofol in 0.50 and 0.25 Cp50asleep had the most extensive effect on the pharyngeal contraction patterns (P < 0.05). The upper esophageal sphincter resting tone was markedly reduced from 83 ± 36 to 39 ± 19 mmHg by propofol (P < 0.001), which differed from isoflurane (P = 0.03). Sevoflurane also reduced the upper esophageal sphincter resting tone from 65 ± 16 to 45 ± 18 mmHg at 0.50 MACawake (P = 0.008). All agents caused a reduced upper esophageal sphincter peak contraction amplitude (P < 0.05), and the reduction was greatest in the propofol group (P = 0.002). Conclusion Subhypnotic concentrations of propofol, isoflurane, and sevoflurane cause an increased incidence of pharyngeal dysfunction with penetration of bolus to the larynx. The effect on the pharyngeal contraction pattern was most pronounced in the propofol group, with markedly reduced contraction forces.