Accidental retropharyngeal dissection extending close to the right common carotid artery during nasotracheal intubation: a case report.

BACKGROUND: Retropharyngeal dissection is a possible complication during nasotracheal intubation. We report a case of a retropharyngeal dissection extending close to the right common carotid artery occurring while inserting a nasotracheal tube. CASE PRESENTATION: An 81-year-old woman, scheduled for laparoscopic and endoscopic cooperative surgery for a duodenal tumor under general anesthesia, sustained submucosal dissection of the retropharyngeal space during nasotracheal intubation. Postoperative computed tomography revealed retropharyngeal tissue injury extending close to the right common carotid artery. The patient was treated with prophylactic antibiotic therapy and discharged uneventfully on postoperative day 13. CONCLUSIONS: Submucosal dissection of the retropharyngeal tissue during nasotracheal intubation has a potential risk of major cervical vessel injury. Therefore, when the tip of the tube cannot be visualized within the oropharynx, clinicians must proceed with caution regarding the expected depth of the tube.

Morphine inhibits cell viability and growth via suppression of vascular endothelial growth factor in human oral cancer HSC-3 cells.

PURPOSE: Although many oral cancer patients require opioids, the effects of morphine and related drugs on oral cancer progression have not been well established. Thus, we examined the effects of morphine exposure on the viability of human oral squamous carcinoma HSC-3 cells and aimed to identify the underlying mechanism. METHODS: We exposed HSC-3 cells to the various concentrations of morphine (0, 0.1, 1, 10, 100, or 1000 µmol/L) for 48 h and, subsequently, evaluated cell viability using the 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyl tetrazolium bromide (MTT) assay and cytotoxicity using the lactate dehydrogenase (LDH) assay. To explore the effects of morphine on cell proliferation further, colony formation assay and cell cycle analysis were performed. Additionally, the intracellular expression of nuclear factor kappa B (NF-κB) was analyzed using flow cytometry, and vascular endothelial growth factor (VEGF)-A was evaluated using human VEGF assay. RESULTS: Morphine exposure reduced cell viability and enhanced cytotoxicity in HSC-3 cells in a concentration-dependent manner. The number of colonies in the morphine-treated groups was significantly lower than that in the control group. Consistent with these results, morphine exposure significantly reduced the concentration of VEGF in the cell culture medium in a concentration-dependent manner. However, our data show that morphine at clinical concentrations (0.1-10 µmol/L) does not affect cell cycle and apoptosis. CONCLUSIONS: Our results suggest that in human oral cancer HSC-3 cells, morphine exposure inhibits cell viability and growth via suppression of VEGF in clinical conditions.

[Exposure to 1 % Sevoflurane for 6 Hours Enhances Proliferation of Human Colon Cancer Cells].

BACKGROUND: Sevoflurane is one of the commonly used volatile anesthetics in cancer patients. The protective effect of sevoflurane preconditioning has raised concerns about whether sevoflurane could act advantageously for survival even of cancer cells. Therefore, we investigated the effects of sevoflurane on proliferation in colon cancer cell lines. METHODS: HCT116 and HT29 cells were plated in 96-well plates at a density of 1 x 10(4) cells/well and incubated overnight. On the next day, cells were exposed to 1% or 2% sevoflurane for 6 hr. After 24 hr recovery, we performed MTT assay. The absorbance of the formazan product was measured at a wavelength of 570 nm using 650 nm as the reference. In addition, to investigate the role of adenosine triphosphate-sensitive potassium (K(ATP)) channels, we conducted the same experiment under co-administration of K(ATP) inhibitor, glibenclamide. RESULTS: Only 1% sevoflurane significantly enhanced cell proliferation compared to the control in HCT116 and HT29 cells. Enhanced proliferation by sevoflurane was completely blocked by co-administration with glibenclamide in HCT116 cells. CONCLUSIONS: We had shown that 1% sevoflurane for 6 hr potentially enhances cell proliferation via K(ATP) channels in cancer cells.

Effect of sevoflurane on human hepatocellular carcinoma HepG2 cells under conditions of high glucose and insulin.

Diabetes mellitus is associated with morbidity and progression of some cancers, such as hepatocellular carcinoma. It has been reported that sevoflurane, a volatile anesthetic agent commonly used in cancer surgery, can lead to lower overall survival rates than those observed when propofol is used to treat cancer patients, and sevoflurane increases cancer cell proliferation in in vitro studies. It has been also reported that glucose levels in rats anesthetized with sevoflurane were higher than those in rats anesthetized with propofol. We investigated the effect of sevoflurane, under conditions of high glucose and insulin, on cell proliferation in the human hepatocellular carcinoma cell line, HepG2. First, we exposed HepG2 cells to sevoflurane at 1 or 2 % concentration for 6 h in various glucose concentrations and then evaluated cell proliferation using the MTT assay. Subsequently, to mimic diabetic conditions observed during surgery, HepG2 cells were exposed to sevoflurane at 1 or 2 % concentration in high glucose concentrations at various concentrations of insulin for 6 h. One-percent sevoflurane exposure enhanced cell proliferation under conditions of high glucose, treated with 0.05 mg/l insulin. Our study implies that sevoflurane may affect cell proliferation in human hepatocellular carcinoma cells in a physiological situation mimicking that of diabetes.

Effects of morphine and fentanyl on 5-fluorouracil sensitivity in human colon cancer HCT116 cells.

Opioids are widely used for perioperative pain management in cancer surgery patients. It has been reported that opioids may alter cancer recurrence or progression; however, there are no published reports regarding the effects of opioids on chemotherapy after cancer surgery. Here we investigated the effects of opioids (morphine or fentanyl) on cell proliferation and 5-fluorouracil sensitivity in the human colon cancer cell line, HCT116. First, we exposed cancer cells to the opioid at various concentrations for 6 or 24 h and evaluated cell proliferation using a MTT assay. Next, to simulate the potential postoperative situation in which anticancer drugs are administered after cancer surgery, cancer cells were incubated with the opioid for 6 or 24 h, followed by treatment with 5-fluorouracil for 48 h. Although fentanyl did not affect cell proliferation, morphine exposure for 6 h enhanced the proliferation. However, sensitivity of HCT116 cells to 5-fluorouracil was not altered in all treatment groups. The current study demonstrated that the opioids commonly used during postoperative periods do not affect 5-fluorouracil sensitivity in human colon cancer HCT116 cells.

Integrins protect cardiomyocytes from ischemia/reperfusion injury.

Ischemic damage is recognized to cause cardiomyocyte (CM) death and myocardial dysfunction, but the role of cell-matrix interactions and integrins in this process has not been extensively studied. Expression of α7ß1D integrin, the dominant integrin in normal adult CMs, increases during ischemia/reperfusion (I/R), while deficiency of ß1 integrins increases ischemic damage. We hypothesized that the forced overexpression of integrins on the CM would offer protection from I/R injury. Tg mice with CM-specific overexpression of integrin α7ß1D exposed to I/R had a substantial reduction in infarct size compared with that of α5ß1D-overexpressing mice and WT littermate controls. Using isolated CMs, we found that α7ß1D preserved mitochondrial membrane potential during hypoxia/reoxygenation (H/R) injury via inhibition of mitochondrial Ca2+ overload but did not alter H/R effects on oxidative stress. Therefore, we assessed Ca2+ handling proteins in the CM and found that ß1D integrin colocalized with ryanodine receptor 2 (RyR2) in CM T-tubules, complexed with RyR2 in human and rat heart, and specifically bound to RyR2 amino acids 165-175. Integrins stabilized the RyR2 interdomain interaction, and this stabilization required integrin receptor binding to its ECM ligand. These data suggest that α7ß1D integrin modifies Ca2+ regulatory pathways and offers a means to protect the myocardium from ischemic injury.

Mitochondria-localized caveolin in adaptation to cellular stress and injury.

We show here that the apposition of plasma membrane caveolae and mitochondria (first noted in electron micrographs >50 yr ago) and caveolae-mitochondria interaction regulates adaptation to cellular stress by modulating the structure and function of mitochondria. In C57Bl/6 mice engineered to overexpress caveolin specifically in cardiac myocytes (Cav-3 OE), localization of caveolin to mitochondria increases membrane rigidity (4.2%; P<0.05), tolerance to calcium, and respiratory function (72% increase in state 3 and 23% increase in complex IV activity; P<0.05), while reducing stress-induced generation of reactive oxygen species (by 20% in cellular superoxide and 41 and 28% in mitochondrial superoxide under states 4 and 3, respectively; P<0.05) in Cav-3 OE vs. TGneg. By contrast, mitochondrial function is abnormal in caveolin-knockout mice and Caenorhabditis elegans with null mutations in caveolin (60% increase free radical in Cav-2 C. elegans mutants; P<0.05). In human colon cancer cells, mitochondria with increased caveolin have a 30% decrease in apoptotic stress (P<0.05), but cells with disrupted mitochondria-caveolin interaction have a 30% increase in stress response (P<0.05). Targeted gene transfer of caveolin to mitochondria in C57Bl/6 mice increases cardiac mitochondria tolerance to calcium, enhances respiratory function (increases of 90% state 4, 220% state 3, 88% complex IV activity; P<0.05), and decreases (by 33%) cardiac damage (P<0.05). Physical association and apparently the transfer of caveolin between caveolae and mitochondria is thus a conserved cellular response that confers protection from cellular damage in a variety of tissues and settings.

Volatile anesthetics protect cancer cells against tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis via caveolins.

BACKGROUND: Volatile anesthetics have a dual effect on cell survival dependent on caveolin expression. The effect of volatile anesthetics on cancer cell survival and death after anesthetic exposure has not been well investigated. The authors examined the effects of isoflurane exposure on apoptosis and its regulation by caveolin-1 (Cav-1). METHODS: The authors exposed human colon cancer cell lines to isoflurane and proapoptotic stimuli and assessed what role Cav-1 plays in cell protection. They evaluated apoptosis using assays for nucleosomal fragmentation, cleaved caspase 3 expression, and caspase activity assays. To test the mechanism, they used pharmacologic inhibitors (i.e., pertussis toxin) and assessed changes in glycolysis. RESULTS: Apoptosis as measured by nucleosomal fragmentation was enhanced by isoflurane (1.2% in air) in HT29 (by 64% relative to control, P < 0.001) and decreased in HCT116 (by 23% relative to control, P < 0.001) cells. Knockdown of Cav-1 in HCT116 cells increased the sensitivity to apoptotic stimuli but not with scrambled small interfering RNA (siRNA) treatment (19.7 ± 0.4 vs. 20.0 ± 0.6, P = 0.7786 and 19.7 ± 0.5 vs. 16.3 ± 0.4, P = 0.0012, isoflurane vs. control in Cav-1 small interfering RNA vs. scrambled small interfering RNA treated cells, respectively). The protective effect of isoflurane with various exposure times on apoptosis was enhanced in HT29 cells overexpressing Cav-1 (P < 0.001 by two-way ANOVA). Pertussis toxin effectively blocked the antiapoptotic effect of isoflurane exhibited by Cav-1 in all cell lines. Cav-1 cells had increased glycolysis with isoflurane exposure; however, in the presence of tumor necrosis factor-related apoptosis-inducing ligand, this increase in glycolysis was maintained in HT29-Cav-1 but not control cells. CONCLUSION: Brief isoflurane exposure leads to resistance against apoptosis via a Cav-1-dependent mechanism.

Cardiac-specific overexpression of caveolin-3 attenuates cardiac hypertrophy and increases natriuretic peptide expression and signaling.

OBJECTIVES: We hypothesized that cardiac myocyte-specific overexpression of caveolin-3 (Cav-3), a muscle-specific caveolin, would alter natriuretic peptide signaling and attenuate cardiac hypertrophy. BACKGROUND: Natriuretic peptides modulate cardiac hypertrophy and are potential therapeutic options for patients with heart failure. Caveolae, microdomains in the plasma membrane that contain caveolin proteins and natriuretic peptide receptors, have been implicated in cardiac hypertrophy and natriuretic peptide localization. METHODS: We generated transgenic mice with cardiac myocyte-specific overexpression of caveolin-3 (Cav-3 OE) and also used an adenoviral construct to increase Cav-3 in cardiac myocytes. RESULTS: The Cav-3 OE mice subjected to transverse aortic constriction had increased survival, reduced cardiac hypertrophy, and maintenance of cardiac function compared with control mice. In left ventricle at baseline, messenger ribonucleic acid for atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) were increased 7- and 3-fold, respectively, in Cav-3 OE mice compared with control subjects and were accompanied by increased protein expression for ANP and BNP. In addition, ventricles from Cav-3 OE mice had greater cyclic guanosine monophosphate levels, less nuclear factor of activated T-cell nuclear translocation, and more nuclear Akt phosphorylation than ventricles from control subjects. Cardiac myocytes incubated with Cav-3 adenovirus showed increased expression of Cav-3, ANP, and Akt phosphorylation. Incubation with methyl-ß-cyclodextrin, which disrupts caveolae, or with wortmannin, a PI3K inhibitor, blocked the increase in ANP expression. CONCLUSIONS: These results imply that cardiac myocyte-specific Cav-3 OE is a novel strategy to enhance natriuretic peptide expression, attenuate hypertrophy, and possibly exploit the therapeutic benefits of natriuretic peptides in cardiac hypertrophy and heart failure.

Opioid-induced preconditioning is dependent on caveolin-3 expression.

We tested the hypothesis that caveolin-3 (Cav-3) is essential for opioid-induced preconditioning in vivo. Cav-3 overexpressing mice, Cav-3 knockout mice, and controls were exposed to myocardial ischemia/reperfusion (I/R) in the presence of SNC-121 (SNC), a δ-selective opioid agonist, or naloxone, a nonselective opioid antagonist. Controls were protected from I/R injury by SNC. No protection was produced by SNC in Cav-3 knockout mice. Cav-3 overexpressing mice showed innate protection from I/R compared with controls that was abolished by naloxone. Our results show that opioid-induced preconditioning is dependent on Cav-3 expression and that endogenous protection in Cav-3 overexpressing mice is opioid dependent.

Disruption of protein kinase A localization using a trans-activator of transcription (TAT)-conjugated A-kinase-anchoring peptide reduces cardiac function.

Localization of protein kinase A (PKA) via A-kinase-anchoring proteins (AKAPs) is important for cAMP responsiveness in many cellular systems, and evidence suggests that AKAPs play an important role in cardiac signaling. To test the importance of AKAP-mediated targeting of PKA on cardiac function, we designed a cell-permeable peptide, which we termed trans-activator of transcription (TAT)-AKAD for TAT-conjugated A-kinase-anchoring disruptor, using the PKA binding region of AKAP10 and tested the effects of this peptide in isolated cardiac myocytes and in Langendorff-perfused mouse hearts. We initially validated TAT-AKAD as a PKA localization inhibitor in cardiac myocytes by the use of confocal microscopy and cellular fractionation to show that treatment with the peptide disrupts type I and type II PKA regulatory subunits. Knockdown of PKA activity was demonstrated by decrease in phosphorylation of phospholamban and troponin I after beta-adrenergic stimulation in isolated myocytes. Treatment with TAT-AKAD reduced myocyte shortening and rates of contraction and relaxation. Injection of TAT-AKAD (1 microM), but not scrambled control peptide, into the coronary circulation of isolated perfused hearts rapidly (<1 min) and reversibly decreased heart rate and peak left ventricular developed pressure. TAT-AKAD also had a pronounced effect on developed pressure (-dP/dt), consistent with a delayed relaxation of the heart. The effects of TAT-AKAD on heart rate and contractility persisted in hearts pretreated with isoproterenol. Disruption of PKA localization with TAT-AKAD thus had negative effects on chronotropy, inotropy, and lusitropy, thereby indicating a key role for AKAP-targeted PKA in control of heart rate and contractile function.

Role of caveolin-3 and glucose transporter-4 in isoflurane-induced delayed cardiac protection.

BACKGROUND: Caveolae are small, flask-like invaginations of the plasma membrane. Caveolins are structural proteins found in caveolae that have scaffolding properties to allow organization of signaling. The authors tested the hypothesis that delayed cardiac protection induced by volatile anesthetics is caveolae or caveolin dependent. METHODS: An in vivo mouse model of ischemia-reperfusion injury with delayed anesthetic preconditioning (APC) was tested in wild-type, caveolin-1 knockout, and caveolin-3 knockout mice. Mice were exposed to 30 min of oxygen or isoflurane and allowed to recover for 24 h. After 24 h recovery, mice underwent 30-min coronary artery occlusion followed by 2 h of reperfusion at which time infarct size was determined. Biochemical assays were also performed in excised hearts. RESULTS: Infarct size as a percent of the area at risk was reduced by isoflurane in wild-type (24.0 +/- 8.8% vs. 45.1 +/- 10.1%) and caveolin-1 knockout mice (27.2 +/- 12.5%). Caveolin-3 knockout mice did not show delayed APC (41.5 +/- 5.0%). Microscopically distinct caveolae were observed in wild-type and caveolin-1 knockout mice but not in caveolin-3 knockout mice. Delayed APC increased the amount of caveolin-3 protein but not caveolin-1 protein in discontinuous sucrose-gradient buoyant fractions. In addition, glucose transporter-4 was increased in buoyant fractions, and caveolin-3/glucose transporter-4 colocalization was observed in wild-type and caveolin-1 knockout mice after APC. CONCLUSIONS: These results show that delayed APC involves translocation of caveolin-3 and glucose transporter-4 to caveolae, resulting in delayed protection in the myocardium.

Effects of landiolol on systemic and cerebral hemodynamics and recovery from anesthesia in patients undergoing craniotomy.

PURPOSE: Maintenance of systemic and cerebral hemodynamics and quick recovery from anesthesia are required for craniotomy. We conducted a prospective randomized study to investigate the effects of continuous infusion of landiolol on hemodynamic responses to various stimuli, changes in systemic and cerebral hemodynamics during anesthesia, and recovery from anesthesia in patients undergoing craniotomy. METHODS: Thirty patients undergoing elective craniotomy were randomly divided into two groups: a landiolol group and a control (saline) group. Landiolol was administered as an infusion rate of 0.125 mg/kg/min for 1 min, followed by an infusion at 0.01-0.04 mg/kg/min until 6 h after the end of anesthesia. Maximal values of heart rate (HR) and systolic blood pressure (SBP) in response to tracheal intubation, pin fixation, the beginning of operation, and extubation were compared between groups. Tissue oxygen index (TOI), mean arterial pressure (MAP), cardiac index (CI), and stroke volume index (SVI) before, during, and at the end of operation were compared between groups. Total doses of fentanyl, interval for the recovery from anesthesia, and incidence of postoperative nausea and vomiting (PONV) were also compared. RESULTS: Maximal values of HR at intubation and pin fixation and of HR and SBP at extubation were significantly less in the landiolol group compared with those in the control group. TOI, MAP, CI, and SVI were similar between groups during anesthesia. Total doses of fentanyl were significantly less in the landiolol group than in the control group. Interval for recovery from anesthesia and incidence of PONV were similar between groups. CONCLUSION: This study indicates that continuous infusion of landiolol suppressed hyperdynamic responses to stimuli during anesthesia while maintaining arterial blood pressure and cerebral oxygen balance during craniotomy. Although landiolol infusion did not affect recovery from anesthesia and incidence of PONV, it reduced intraoperative requirement of fentanyl.

Anesthetic management of bidirectional cavopulmonary shunt in a patient with pulmonary atresia with intact ventricular septum associated with sinusoidal communications.

Pulmonary atresia with intact ventricular septum (PAIVS) is sometimes associated with coronary artery anomalies, including right ventricle (RV)-to-coronary artery fistulas (sinusoidal communications), coronary artery stenoses, and coronary artery occlusions. In some cases, the coronary circulation depends entirely or partly on the desaturated systemic venous blood supply from the RV. Under these circumstances, decompression of the RV can result in fatal myocardial ischemia. A 6-month-old boy, diagnosed with PAIVS associated with sinusoidal communications, underwent a bidirectional cavopulmonary shunt procedure under venoarterial cardiopulmonary bypass (CPB). During CPB, to prevent RV decompression, we maintained right atrial pressure above 5 mmHg and used a pump perfusion rate of 30%-40% of the calculated value based on body surface area. Although electrocardiography showed slight ST depression and bradycardia, myocardial contractility after weaning from CPB was adequate to maintain the circulation with the administration of dobutamine and atrial pacing. In patients with PAIVS and RV-dependent coronary circulation, it is important to maintain coronary artery perfusion throughout the period of anesthesia.

Evaluation of relatively low dose of oral transmucosal ketamine premedication in children: a comparison with oral midazolam.

BACKGROUND: Oral Transmucosal ketamine (lollipop) has been shown to be an effective, harmless preoperative medication for children. However, its efficacy was not compared with commonly used premedication drugs. We, therefore, compared the efficacy of oral transmucosal ketamine with oral midazolam for premedication in children. METHODS: Fifty-five children (2-6 years of age) were randomized to receive orally either a lollipop containing 50 mg of ketamine (the group K; n = 27) or syrup containing 0.5 mg.kg(-1) of midazolam (the group M; n = 28) before minor surgery. A five points-sedation score (1 = asleep to 5 = agitated; scores 2 and 3 were defined as 'effective') on arrival in the operating room and a three points-acceptance score of separation from the parents and a three points-mask cooperation score at induction of anesthesia (1 = easy to 3 = markedly resistant; score 3 was defined as 'poor') were used. RESULTS: Sedation scores in group K were significantly higher than those in group M (P = 0.012), and the incidence of 'effective' in sedation was significantly lower in group K than in group M (P = 0.036). The incidence of 'poor' at separation from the parents and for mask cooperation was significantly higher in group K than in group M (P = 0.017, P = 0.019, respectively). CONCLUSION: These results indicate that a relatively low dose of oral transmucosal ketamine premedication provides no benefits over oral midazolam in children.

Anesthetic management of a 9-year-old child undergoing resection of a tracheal tumor.

Primary tracheal tumors in children are rare. We report the anesthetic management of a 9-year-old child undergoing resection of a midtracheal tumor obstructing approximately 73% of the tracheal lumen. To prepare for any possible airway emergency during the induction and maintenance of anesthesia, we ascertained preoperatively that a mini-tracheotomy tube could be inserted at the distal portion of the tracheal lesion. Oxygenation and ventilation were adequately maintained throughout the period of anesthesia. Anesthetic management for tracheal tumor resection should reflect the location of the tumor and the degree of tracheal obstruction.

[Lockjaw caused by induction of anesthesia in a volunteer bone marrow donor].

A 43-year-old healthy female volunteer donor was scheduled for bone marrow harvesting. In the operating room her mouth opening was ascertained to be 5 cm. Anesthesia was induced with thiamylal 250 mg, fentanyl 0.1 mg and vecuronium 6 mg i.v. Her mouth opening was found reduced to 2 cm that was not improved by additional vecuronium 2 mg. A consulted oral surgeon diagnosed temporomandibular disorder. After she was awakened once with resumed mouth opening, anesthesia was reinduced with a bite block placed and with her jaw held open by the oral surgeon, which brought the same results. Laryngoscopy was performed with the jaw forcefully opened and with cricoid pressure applied and the trachea was intubated. The surgical procedure and anesthesia thereafter were uneventful. Postoperative MRI was coincident with the diagnosis of temporomandibular disorder. It was speculated that in the donor patient with preexisted type II temporomandibular disorder, muscle relaxation induced by anesthesia caused the mandibular head fall behind the articular disk and dislocated the disk forwardly ending up in closed lock of temporomandibular joint.

[Spinal anesthesia using hyperbaric bupivacaine HCl for cesarean section].

BACKGROUND: We performed this prospective study to determine the proper amount of hyperbaric bupivacaine hydrochloride as a spinal anesthetic agent for cesarean section. METHODS: The parturients were randomly allocated to receive one of four spinal agents in a blind manner; tetracaine 10 mg (control), bupivacaine 10, 12.5 and 15 mg. Morphine HCl 0.1 mg was added to each agent and the total volume was adjusted to 3.1 ml with 10% glucose solution. RESULTS: All the four spinal agents provided an adequate analgesic level (T 5) without serious complications. Among the three dosages of bupivacaine, the time interval requiring for anesthetic level to reach T 5 tended to be shorter with a larger amount of bupivacaine. The incidence of intraoperative supplemental analgesic and hypotension and the dosage of ephedrine used to treat hypotension were greater in the patients anesthetized with tetracaine 10 mg than in those anesthetized with bupivacaine 10 mg, which is equipotent to tetracaine 10 mg. CONCLUSIONS: 1. As a spinal anesthetic agent for cesarean section, hyperbaric bupivacaine is superior to tetracaine. 2. Hyperbaric bupivacaine 10 mg, 12.5 mg or 15 mg can be used safely and effectively as a spinal agent for cesarean section. 3. High dose bupivacaine is recommended in an urgent case, and low dose bupivacaine is recommended when maternal hypotension must be strictly avoided.