Modulation of propofol on the effects of blood pressure and firing activity of related neurons in the medulla.

Many studies have demonstrated that the ventrolateral medulla (VLM) plays an important role in the maintenance of systemic arterial pressure (SAP) and vascular tone. The VLM is divided into rostral (RVLM) and caudal (CVLM) portions which play opposing roles in regulating cardiovascular functions. The purposes of this study are to explore the relationship of fibers projecting between the RVLM and CVLM, and to investigate the effect of propofol (PPF, 2 mg/kg), an anesthetic agent, on modulating their neuronal firing rate (NFR). Forty-four adult cats were anaesthetized intraperitoneally with urethane (400 mg/kg) and alpha-chloralose (40 mg/kg). The femoral artery was cannulated to allow monitoring of SAP and heart rate (HR). The femoral vein was cannulated for intravenous drug administration. Microinjection of glutamate (Glu, 3.0 nmol/30 nl), kynurenic acid (Kyn, 3.0 nmol/30 nl), gamma-aminobutyric acid (GABA, 4.0 nmol/30 nl), or bicuculline (Bicu, 4.0 nmol/30 nl) into the RVLM produced SAP increases or decreases, but did not significantly change the NFR in the CVLM. This occurred even after intravenous administration of PPF. This shows that there are few fiber projections from the RVLM to the CVLM. Conversely, microinjection of Glu, Kyn, GABA or Bicu into the CVLM produced SAP changes, and the NFR in the RVLM was significantly changed. These changes were more significant after intravenous administration of PPF. These results show that there are more fibers projecting from the CVLM to the RVLM and fewer fibers projecting from the RVLM to the CVLM to affect the SAP and its NFR.

Inhibition of the cyclic adenosine monophosphate pathway attenuates neuropathic pain and reduces phosphorylation of cyclic adenosine monophosphate response element-binding in the spinal cord after partial sciatic nerve ligation in rats.

BACKGROUND: Recent reports have identified a role for cyclic adenosine monophosphate (cAMP) transduction in nociceptive processing. Spinal activation of the cAMP induced gene transcription through the activation of protein kinase A and cAMP response element-binding protein (CREB). Intrathecal injection of protein kinase A inhibitor reversed the mechanical hyperalgesia, whereas injection of CREB antisense attenuated tactile allodynia caused by partial sciatic nerve ligation (PSNL) in rats. In the present study, we aimed to assess the effects of spinal cAMP transduction on the nociceptive processing in a chronic neuropathic pain model. METHODS: PSNL was performed in male Sprague-Dawley rats 1 wk after intrathecal catheterization. Nociception to mechanical and thermal stimuli was assessed at the hindpaw 2 h, 3, 7, and 14 days after PSNL. The effects of adenylate cyclase inhibitor, SQ22536 (0.7 mumol, intrathecal) on these nociceptions were evaluated. Changes in the expression and immunoreactivity of CREB and its phosphorylated proteins (CREB-IR and pCREB-IR) in the dorsal horn of the spinal cord were also measured. RESULTS: The expression of CREB-IR and pCREB-IR proteins was shown to increase for 2 wk after PSNL. The increase in pCREB was partially reversed by the blockade of the cAMP pathway in the early 3 days, with a parallel increase in mechanical and thermal withdrawal thresholds. CONCLUSION: These results revealed the possible contribution of an increase in pCREB to the PSNL-induced tactile allodynia and thermal hyperalgesia. Modulation of the cAMP pathway may be clinically relevant if early intervention can be achieved in patients with chronic neuropathic pain.

Inhibitory effects of propofol on neuron firing activities in the rostral ventrolateral medulla.

The effect of propofol on neuronal activity in the rostral ventrolateral medulla (RVLM) is not well established. Therefore, we performed extracellular recording on neurons of the RVLM to investigate neuronal activity before and after administration of intravenous propofol. The mean systemic arterial pressure (MSAP), heart rate and integrated neuronal firing rate (INFR) in the RVLM were continuously recorded in anesthetized cats before and after intravenous injection of 2 mg/kg propofol or supplemental injections of 1, 2 and 4 mg/kg propofol that were given respectively. Additionally, we compared the MSAP, heart rate (HR), and INFR in the RVLM following intravenous injection of 2 mg/kg propofol or 12.5 microg/kg nitroprusside. Neuronal firing was dose-dependently and reversibly inhibited after the supplemental doses of 1, 2 and 4 mg/kg propofol. The control INFR was 14.2 +/- 9.9 Hz, and this decreased to 12.1 +/- 9.4 Hz after the first dose of propofol (P = 0.085 vs. control), and further decreased to 9.3 +/- 7.7 Hz (P = 0.001 vs. control) and 7.5 +/- 7.7 Hz (P < 0.001 vs. control) after the second and third doses of propofol, respectively. Besides, SAP and HR were dose-dependently decreased by propofol as well. However, the effects of propofol and nitroprusside on neuronal activity in the RVLM differed. Propofol inhibited neuronal firing, whereas nitroprusside activated neuronal firing. In conclusion, propofol may dose-dependently inhibit spontaneous neuronal activity and the baroreflex in the RVLM.

Serotonin modulates glutamate action in the medulla to regulate cardiovascular functions in cats.

We examined the effects of serotonin (5-HT) on cardiovascular responses and blood flows in the right common carotid artery (RCCA), superior mesenteric artery (SMA) and right femoral artery (RFA), stimulated by glutamate (Glu) in the dorsomedial medulla (DM), rostral ventrolateral medulla (RVLM) and caudal ventrolateral medulla (CVLM). Microinjection of Glu into the DM produced increases in systemic arterial pressure (SAP) and flows in the RCCA and RFA, and decrease in flow in the SMA. Microinjection of Glu into the RVLM produced increases in SAP and decreases in flows in the RCCA, SMA and RFA. Prior microinjections of 5-HT into the same sites attenuated all the Glu-induced responses. Microinjection of Glu into the CVLM produced decreases in SAP and flows in the RCCA, SMA and RFA. These decreases were potentiated by prior injection of 5-HT. These findings suggest that 5-HT modulates the cardiovascular and blood flow responses induced by Glu in the medulla.

The nNos/cGMP mediation of the depressor response to NMDA receptor stimulation in the caudal ventrolateral medulla.

Using in vivo voltammetry to directly measure extracellular nitric oxide (NO) levels, our previous studies suggested that the neuronal NO synthase (nNOS) and cyclic guanosine monophosphate (cGMP) signal transducing systems are involved in the cardiovascular responses elicited by activation of N-methyl-D-aspartate (NMDA) receptors in the rostral ventrolateral medulla. In this study, we examined if the depressor responses elicited by activation of NMDA receptors in the caudal ventrolateral medulla (CVLM) also depend on the actions of nNOS and soluble guanylyl cyclase. In anesthetized cats, microinjection of NMDA into the CVLM produced hypotension and bradycardia associated with NO formation. These NMDA-induced responses were attenuated by prior injections of 2-amino-5-phosphonopentanoate (a NMDA receptor competitive antagonist), 7-nitroindazole (a nNOS inhibitor) and 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (an inhibitor of soluble guanylyl cyclase). These findings suggest that NO is also involved in the NMDA-induced depressor responses of the CVLM.

Chemical burn caused by povidone-iodine alcohol solution--a case report.

Burns associated with chemical disinfectants for skin preparation are rare. Skin irritation and maceration associated with pressure factors may contribute to its occurrence. We report a 24-year-old female with thyroid tumor who was admitted for subtotal thyroidectomy. After anesthetic induction, the patient was placed in the supine position with the trunk elevated to 20 degree. The skin over the anterior neck was sterilized with 10% Povidone-iodine (PI) alcohol solution. After a 3-hour surgery, the patient complained of burning pain over the back at the recovery room. Physical examination revealed a 9 x 11 cm area of skin lesion partially thickened amid on the middle of the back suggestive of chemical burn. After conservative treatment, she was discharged uneventfully 4 days later. Upon follow-up, the wound was seen to heal with minimal scarring within 3 weeks.

Short-term inhalation of sevoflurane during induction of general anesthesia can inhibit the A-line ARX index response to intubation: a randomized trial.

BACKGROUND: Monitoring hypnotic depth is used to prevent awareness during general anesthesia. We used the A-line ARX index (AAI) to assess the effect of shortterm inhalation of sevoflurane in the prevention of intubation-induced inadequate hypnotic depth during anesthetic induction. METHODS: Thirty patients were randomly divided into the sevoflurane and non-sevoflurane groups, both of which were given 3 µg kg⁻¹ fentanyl, 4 mg kg⁻¹ thiamylal, and 0.2 mg kg⁻¹ cis-atracurium intravenously to induce general anesthesia. The sevoflurane group then inhaled 6% sevoflurane and 4 L/min O2 for 3 minutes, whereas the non-sevoflurane group was given 4 L/min O2 alone. Both groups were intubated 3 minutes after induction. Measurements of the AAI, non-invasive blood pressure, and heart rate were performed every minute, starting 3 minutes prior to induction until 9 minutes after intubation. RESULTS: Intubation induced a significant AAI elevation in the non-sevoflurane group (47.13 ± 20.88, 48.13 ± 20.05, 40.87 ± 15.86 and 31.27 ± 15.26 at 1, 2, 3 and 4 minutes after intubation, respectively, vs. 17.67 ± 6.44 at 3 minutes after induction; p < 0.05), whereas the AAI remained unchanged for the sevoflurane group following intubation. Moreover, the non-sevoflurane group demonstrated higher AAI values after intubation compared with the sevoflurane group. There were no significant differences in blood pressure and heart rate between the two groups throughout the study. CONCLUSION: Adding 6% sevoflurane with 4 L/min O2 for 3 minutes during the induction period prevented inadequate hypnotic depth caused by intubation but was not sufficient to inhibit fluctuations in hemodynamics.

Airway obstruction by a metastatic mediastinal tumor during anesthesia.

A case of low back pain syndrome was diagnosed due to spinal metastasis with unknown primary origin. During anesthesia for surgical stabilization, unexpected airway obstruction occurred after endotracheal intubation. Fiber-optic bronchoscopic examination showed narrowing of the trachea and main bronchi caused by extrinsic compression. After administration of neostigmine to reverse neuromuscular blockade, the patient resumed spontaneous breath. Airway obstruction was relieved thereafter. The extrinsic lesion was diagnosed as mediastinal lung cancer. The mechanism and management of this airway compromise caused by mediastinal tumor is discussed.

Propofol ensures a more stable A-line ARX index than thiopental during intubation.

BACKGROUND: The A-line autoregressive modelling with exogenous input index (AAI) is a new method of assessing depth of anesthesia. We examined the effects of tracheal intubation on the AAI and hemodynamics during induction of anesthesia with propofol compared with thiopental in patients aged over 50 yr. METHODS: 40 patients scheduled for a laminectomy, posterior spinal fusion, vertebroplasty, or total hip replacement, ASA physical status I or II and aged over 50 yr, were randomly divided into two groups. Thiopental 5 mg.kg(-1) iv, fentanyl 2.5 microg.kg(-1) iv, and rocuronium 0.7 mg.kg(-1) iv were used in the thiopental group (n = 20) for anesthetic induction; the same protocol was used in the propofol group (n = 20) except that 2 mg.kg(-1) propofol iv was given instead of thiopental. The AAI, non-invasive blood pressure, and heart rate were measured every minute before induction for three minutes, at 1.5 min post-induction, and then each minute post-intubation for eight minutes. RESULTS: The AAI increased significantly at one and two minutes after intubation in the thiopental group (to 56.5 +/- 18.6 at 1 min and 44.7 +/- 18.7 at 2 min after intubation vs 19.9 +/- 7.5 at 1.5 min after induction; P < 0.05). Thereafter, AAI values gradually decreased three minutes after intubation. The AAI was inhibited continuously after intubation in the propofol group, and no significant elevation was seen. CONCLUSION: Our results, using the AAI to monitor anesthetic depth during induction and tracheal intubation, suggest that at equipotent doses propofol provided a more stable level of anesthesia than did thiopental.

High satisfaction with problem-based learning for anesthesia.

BACKGROUND: The aim of this study was to compare students' satisfaction between problem-based learning (PBL) and lecture-based traditional teaching of anesthesia. METHODS: One hundred and thirty-seven fifth-year medical students were enrolled in a course which used a hybrid curriculum for teaching about anesthesia. The hybrid curriculum included 9 essential lectures and 3 related PBL case discussions. A Linkert 5-point scale was used for to assess students' satisfaction levels between PBL and lecture-based traditional teaching. Data were collected through a year-end questionnaire over 2 academic years from 2002 to 2003. Scores regarding the satisfaction levels between these 2 teaching methods were analyzed using a 2-sided paired t-test. RESULTS: Most students preferred PBL over the lecture-based traditional teaching in the following 6 aspects: learning about anesthesia, understanding other medical knowledge, being interested in and motivated to learn, training for future work, training of personal abilities, and being confident and satisfied with the teaching method (p < 0.05). However, traditional teaching was superior to PBL in enhancing the speed of learning with greater understanding of a basic knowledge of anesthesia, as well as in providing more solid content with understanding of a greater number of anesthetic techniques (p < 0.05). Satisfaction levels with this curriculum did not generally differ between students enrolled in different classes in 2002 and 2003. CONCLUSIONS: Although the assessment tools and content of PBL need to be modified, implementation of PBL for teaching anesthesia showed satisfactory results.

Rocuronium-induced generalized spontaneous movements cause pulmonary aspiration.

Rapid-sequence induction with cricoid pressure is a standard procedure for inducing anesthesia in patients with a potentially full stomach. During the induction period, if the patient develops generalized movements of the body, the pressure level of the cricoid may change unexpectedly. As a result, the increase in intragastric pressure may cause gastric regurgitation and consequent pulmonary aspiration. Rocuronium has been widely used as an alternative to succinylcholine during the induction of anesthesia. However, most patients who received rocuronium complained of severe burning pain in their arm during intravenous injection. Even after the administration of the induction agents, rocuronium injection can also cause withdrawal of the hand or other generalized movements of the body. We describe a case of gastric regurgitation with pulmonary aspiration following generalized spontaneous movements associated with rocuronium injection in a girl who received pediatric emergent surgery.

Propofol inhibits neuronal firing activities in the caudal ventrolateral medulla.

BACKGROUND: Propofol is a potent intravenous anesthetic. The action of propofol on the medullary depressor area, the caudal ventrolateral medulla (CVLM), has not been well established. We therefore performed extracellular recordings to study the neuronal activity of the CVLM in cats before and after intravenous propofol administration, to investigate its influence on neuronal firings. METHODS: Experiments were performed on 31 cats anaesthetized with a mixture of alpha-chloralose and urethane administered intraperitoneally. Mean systemic arterial pressure, heart rate, and the neuronal firing (NF) rate were continuously recorded before and after intravenous injection of a single dose of 2 mg x kg(-1) propofol or separate supplemental doses of 1, 2, and 4 mg x kg(-1) propofol until those parameters had returned to the premedication level. RESULTS: Propofol dose-dependently and reversibly inhibited the NF rate after the supplemental doses of 1, 2, and 4 mg x kg(-1) propofol. The control NF rate of 17.9 +/- 8.6 Hz was depressed to 15.8 +/- 8.5 Hz after the first dose of propofol (p < 0.05 vs. the control), and was further depressed to 12.8 +/- 8.3 Hz (p < 0.05 vs. the control) and 10.0 +/- 7.9 Hz (p < 0.05 vs. the control) after the second and the third doses of propofol, respectively. CONCLUSION: The dose-dependent inhibition of the spontaneous neuronal firing rate is the main pharmacological action of propofol in the caudal ventrolateral medulla of cats.