Keum Young So

Carbachol regulates pacemaker activities in cultured interstitial cells of Cajal from the mouse small intestine

We studied the effect of carbachol on pacemaker currents in cultured interstitial cells of Cajal (ICC) from the mouse small intestine by muscarinic stimulation using a whole cell patch clamp technique and Ca2+-imaging. ICC generated periodic pacemaker potentials in the current-clamp mode and generated spontaneous inward pacemaker currents at a holding potential of–70 mV. Exposure to carbachol depolarized the membrane and produced tonic inward pacemaker currents with a decrease in the frequency and amplitude of the pacemaker currents. The effects of carbachol were blocked by 1-dimethyl-4-diphenylacetoxypiperidinium, a muscarinic M3 receptor antagonist, but not by methotramine, a muscarinic M2 receptor antagonist. Intracellular GDP-β-S suppressed the carbachol-induced effects. Carbachol-induced effects were blocked by external Na+-free solution and by flufenamic acid, a non-selective cation channel blocker, and in the presence of thapsigargin, a Ca2+-ATPase inhibitor in the endoplasmic reticulum. However, carbachol still produced tonic inward pacemaker currents with the removal of external Ca2+. In recording of intracellular Ca2+ concentrations using fluo 3-AM dye, carbachol increased intracellular Ca2+ concentrations with increasing of Ca2+ oscillations. These results suggest that carbachol modulates the pacemaker activity of ICC through the activation of non-selective cation channels via muscarinic M3 receptors by a G-protein dependent intracellular Ca2+ release mechanism.

Bradycardia during laparoscopic surgery due to high flow rate of CO2 insufflation.

Pneumoperitoneum, using carbon dioxide (CO2), is used to assist laparoscopic surgery by making distension of abdominal cavity and splitting up its content, which improves visualization. However, artificial pneumoperitoneum may cause complications, such as bradycardia and even cardiac arrest, which are originated from increased abdominal pressure and CO2 retention [1]. We experienced severe bradycardia after CO2 insufflation with high flow rate during laparoscopic gynecological surgery. A 59-year-old woman (154 cm and 56 kg), without any remarkable past history except well controlled hypertension, has come to take a laparoscopic colpopexy. Midazolam 2.5 mg was administered intramuscularly, 30 minutes before she transferred to the operation room. On arrival, initial blood pressure (BP) and heart rate (HR) were 120/90 mmHg and 65 beats per minute (bpm), respectively, and peripheral oxygen saturation (SpO2) was 98%. Propofol 120 mg and rocuronium 40 mg were injected for induction. Intubation was done with 7.0 mm endotracheal tube, and tidal volume (9 ml/kg) and respiratory rate were regulated to maintain a normal end-tidal CO2 (ETCO2). Anesthesia was maintained with 50% oxygen and sevoflurane 2 vol% and remifentanil was administered as a 0.05 µg/kg/min infusion, simultaneously. ETCO2 was maintained about 35 mmHg and peak inspiratory pressure (PIP) was 15 cmH2O. Trocar (SAFE PASS TROCARR, Vaxcon co., Incheon, Korea), size of 11 mm, was inserted to 1 cm below the umbilicus to induce pneumoperitoneum. CO2 insufflation was started with an insufflator (Insufflator ML-GX, MGB Endoscope Co. Ltd, Seoul, Korea), and then her BP and HR suddenly decreased to 80/60 mmHg and 42 bpm, respectively. PIP has increased to 20 cmH2O, but ETCO2 and SpO2 did not change. It was thought to be a consequence of peritoneal stretching, owing to pneumoperitoneum, so CO2 insufflation was seized. Remifentanil infusion was stopped and atropine 0.5 mg was injected. Then, BP and HR became 120/80 mmHg and 60 bpm, respectively. CO2 insufflation was started again, but bradycardia and hypotension developed yet again, and BP and HR decreased to 62/32 mmHg and 23 bpm, respectively. Pressure limit of insufflator kept 12 cmH2O during CO2 insufflation, but we found the flow rate of CO2 insufflation was too high (20 L/min). Her vital signs became stabilized again after stopping insufflator and hyperventilation with 100% O2. Flow rate was adjusted to start as 1 L/min and increased to 3 L/min after 2 minutes. While adequate pneumoperitoneum was achieved, vital signs were stable without hypotension or bradycardia. There were no sudden bradycardia or hypotension during surgery and she was transferred to the recovery room without any hazardous event. It is well known that laparoscopic surgery, using CO2 to make a pneumoperitoneum, has risks of pathophysiological cardiovascular changes, such as severe bradycardia, arrhythmia, and cardiac arrest requiring cardiopulmonary resuscitation [1]. Causes of such alteration are known to be associated with vagal-mediated cardiovascular reflex initiated by rapid peritoneum distension due to insufflation or gas embolism [2]. Limiting of intra-abdominal pressure (IAP) below 12-15 mmHg during insufflation is known to be effective to prevent pathophysiological changes of pneumoperitoneum [1]. Even though pressure limitations of insufflator were 12 mmHg in our cases, severe bradycardia has developed after insufflation. Gas embolism was ruled out because there were no changes in ETCO2 and SpO2 [1]. Arrhythmias developed after rapid stretching of peritoneum are transient and well respond to reduction of IAP [2], and our patients had recovered soon after stopping insufflations and hyperventilation with 100% O2; thus, we concluded the arrhythmias are a consequence of peritoneal distension due to rapid increase of IAP after CO2 insufflation with high flow rate. But, it was a question that how high flow rate of insufflator could affect the IAP in the circumstances of maintaining acceptable pressure limit. We thought the system of insufflators was the clue. Jacobs et al. has reported the insufflations performance and patient safety during laparoscopy [3]. Insufflator works effectively when balance of pressure, resistance and flow in system is established. Accordingly, gas flow from insufflator patients abdomen follows the Hagen-Poiseuilles law theoretically [3]: where V = gas flow, π = factor Pi, r = radius, 8 = constant, η = viscosity, l = length, and ΔP = pressure difference. As the Hagen-Poiseuilles law states, gas flow rises in proportion to a rise in pressure, and depends on the smallest diameter of the system [3,4]. Thus, pressure will rise to keep a high flow rate when gas passes through high resistance channel of trocar, such as luer lock connector. Consequently, IAP will rise quickly to keep up the velocity if insufflator is regulated to keep a high flow rate as 20 L/min from the start of pneumoperitoneum. And more, insufflator that supports high flow rate usually uses over-pressure insufflation principle, which puts pressure much greater than preset value when starting insufflation [3]. Over-pressure system supply pressure beyond the preset value when starting of pneumoperitoneum and pressure decreased during insufflation break intermittently, until IAP reaches to the nominal pressure that has usually been preset to 12 mmHg [3,4]. As such, even if the preset value is limited to 12 mmHg, peak pressure of IAP will exceed the limit in an instant to keep up the fixed flow rate. Such repetitive exceeded IAP may stretch the peritoneum and stimulate vegal responses. Cho and Min [1] had reported a similar case of severe bradycardia, which the flow rate was 50 L/min when the recommended flow rate was 1 L/min. Dhoste et al. [5] has reported that gradual abdominal insufflation to 12 mmHg with a slow flow rate of 1 L/min was associated with cardiovascular stability in elderly ASA III patients. We also experienced hemodynamic stability when using a gradual increase of flow rate from 1 L/min. So, we consider it is an appropriate start from the low flow rate as 1L/min in the beginning of pneumoperitoneum. In conclusion, insufflation with high flow rate when establishing artificial pneumoperitoneum may increase IAP instantaneously and unexpected cardiovascular changes, such as hypotension, bradyarrhythmia or cardiac arrest, may occur. Therefore, not only maintaining IAP below 12-15 mmHg, but also keeping slow insufflation when establishing pneumoperitoneum is important and essential.

Effects of lidocaine, ketamine, and remifentanil on withdrawal response of rocuronium

Background Rocuronium has been well known to produce withdrawal response in 50-80% patients when administered intravenously. Several drugs are administered prior injection of rocuronium to prevent the withdrawal response. We compared the preventive effect of lidocaine, ketamine, and remifentanil on the withdrawal response of rocuronium. Methods A total of 120 patients undergoing various elective surgeries were enrolled. Patients were allocated into 4 groups according to the pretreatment drugs (Group N, normal saline; Groups L, lidocaine 40 mg; Group K, ketamine 0.5 mg/kg; Group R, remifentanil 1 µg/kg). Patients received drugs prepared by dilution to 3 ml volume before injection of rocuronium. Withdrawal responses after injection of rocuronium were graded on a 4-point scale. Hemodynamic changes were observed before and after administration of pretreatment drugs and after endotracheal intubation. Results Incidence of withdrawal response was significantly lower in group L (20%), group K (30%), and group R (0%), than group N (87%). Severe withdrawal response was observed in 5 of the 30 patients (17%) in group L, and in 9 of the 30 patients (30%) in group K. There was no severe withdrawal response in group R. Mean blood pressure and heart rate were significantly decreased in group R compared to other groups. Conclusions It seems that remifentanil (1 µg/kg intravenously) was the strongest and most effective in prevention of withdrawal response after rocuronium injection among the 3 drugs.

Clinical evaluation of a newly designed fluid warming kit on fluid warming and hypothermia during spinal surgery

Background The Mega Acer Kit® (MAK) is a newly designed heated and humidified breathing circuit that warms fluid passing through the circuit lumen. In this study, we investigated the systems efficacy for the perioperative prevention of hypothermia and fluid warming. Methods Ninety patients undergoing spinal surgery were enrolled in this study and randomly assigned to 3 groups based on the fluid warming device used: no fluid warming system (Group C, n = 30), via a Standard Ranger (Group R, n = 30), or via the MAK (Group M, n = 30). Distal esophageal temperatures (Teso) and infusion fluid temperature (TF) were recorded at 15 min intervals for duration of 180 min during surgery. If Teso was < 35.0℃, a forced-air convective warming device was used. Results Final Teso values were 34.8 ± 0.3℃, 35.1 ± 0.1℃, and 35.8 ± 0.3℃ in groups C, R, and M, respectively (P < 0.01). Teso was significantly higher in group M when compared with that in groups C and R throughout the study period (P < 0.05). The number of patients requiring a forced-air convective warming device was significantly lower in group M (n = 0) when compared with that in groups R (n = 17) and C (n = 30) (P < 0.05). The final infusion fluid temperature was higher in group M when compared with that in groups C and R throughout the study period (35.4 ± 1.0 vs. 23.0 ± 0.3 and 32.8 ± 0.6℃; P < 0.01). Conclusions The MAK is more effective for preventing hypothermia and for warming fluid than the Standard Ranger.

Effect on thermoregulatory responses in patients undergoing a tympanoplasty in accordance to the anesthetic techniques during PEEP: a comparison between inhalation anesthesia with desflurane and TIVA

Background It has been known that positive end-expiratory pressure (PEEP) increases the vasoconstriction threshold by baroreceptor unloading. We compared the effect on the thermoregulatory responses according to anesthetic techniques between an inhalation anesthesia with desflurane and a total intravenous anesthesia (TIVA) with propofol and reminfentanil when PEEP was applied in patients undergoing tympanoplasty. Methods Forty-six patients with a scheduled tympanoplasty were enrolled and the patients were divided in two study groups. Desflurane was used as an inhalation anesthetic in group 1 (n = 22), while TIVA with propofol and remifentanil was used in group 2 (n = 24). PEEP was applied by 5 cmH2O in both groups and an ambient temperature was maintained at 22-24℃ during surgery. The core temperature and the difference of skin temperature between forearm and fingertip were monitored for about 180 minutes before and after the induction of general anesthesia. Results The final core temperature was significantly higher in group 2 (35.4 ± 0.7℃) than in group 1 (34.9 ± 0.5℃). Peripheral thermoregulatory vasoconstriction was found in 5 subjects (23%) in group 1 and in 21 subjects (88%) in group 2. The time taken for reaching the thermoregulatory vasoconstriction threshold was 151.4 ± 19.7 minutes in group 1 and 88.9 ± 14.4 minutes in group 2. Conclusions When PEEP will be applied, anesthesia with TIVA may have more advantages in core temperature preservation than an inhalation anesthesia with desflurane.

Radiofrequency Thermal Ablation as a Treatment for Symptomatic Bertolotti's Syndrome: A Case Report

Background Bertolottis syndrome may be a risk factor for low back pain. Findings A 58-year-old female patient with chronic low back and left buttock pain due to Bertolottis syndrome experienced incomplete relief with L5 selective transforaminal epidural block. A local anesthetic and corticosteroid injection into the pseudoarticulation and at the lower and upper pseudoarticular margin at one week intervals resulted in temporary relief. Pulsed radiofrequency was performed at the upper and lower pseudoarticular margins. She had complete relief of pain after six months. Conclusion Pulsed radiofrequency treatment may be useful for patients with Bertolottis syndrome.

Effect of intraoperative infusion of sufentanil versus remifentanil on postoperative shivering in Korea: a prospective, double-blinded, randomized control study

Background/aim The number of published papers that compare the incidence of sufentanil- and remifentanil-related postoperative shivering is insufficient. We investigated the incidence of postoperative shivering after total intravenous anesthesia with either sufentanil or remifentanil in patients who underwent elective surgery. Materials and methods Eighty-three patients, with a physical status classified as American Society of Anesthesiologists I or II, were randomly allocated to either the remifentanil–propofol (RP group, n = 40) or sufentanil–propofol (SP group, n = 43) group. The primary endpoint was the incidence of postoperative shivering 1 h after entering the recovery room. The secondary endpoints were intraoperative core temperatures of the esophagus and tympanic membrane at 30 min after the induction of anesthesia and at the end of surgery. Results The overall postoperative shivering incidence was not significantly different between the RP (15%) and SP (11.6%) groups (P = 0.651). The intraoperative temperatures and their changes (the temperature 30 min after induction minus that after surgery) as measured at the distal esophagus and tympanic membrane were not significantly different between the RP and SP groups. Conclusion The incidence of postoperative shivering related to sufentanil was less than that related to remifentanil, with no significant differences in the intraoperative core temperatures.

Effect of dexamethasone on the onset time and recovery profiles of cisatracurium

Background The effect of dexamethasone injection on cisatracurium-induced neuromuscular block was compared according to different injection time points. Methods One hundred seventeen patients were randomly assigned to three groups: 8 mg of dexamethasone injected intravenously 2–3 h before anesthesia (group A), just before anesthesia induction (group B), and at the end of surgery (control group). Three minutes after anesthesia induction, intubation was performed without neuromuscular blockers, and acceleromyography was initiated. All patients received 0.05 mg/kg cisatracurium; the onset time and recovery profiles were recorded. Results Eighty patients were finally enrolled. The onset time (median [interquartile range], seconds) was significantly hastened in group A (520.0 [500.0–560.0], n = 30) compared to that in group B (562.5 [514.0–589.0], n = 22) (P = 0.008) and control group (586.5 [575.0–642.5], n = 28) (P < 0.001). The onset time in group B was faster than the control group (P = 0.015). The recovery time [mean (95% CI) minutes] was significantly hastened in group A [28.5 (27.3–29.6)] compared to that in group B [32.3 (31.0–33.6)] (P < 0.001) and control group [30.9 (29.9–31.8)] (P = 0.015). The total recovery time was significantly hastened more in group A [47.1 (45.5–48.6)] than group B [52.8 (51.6–54.0) minutes] (P < 0.001) and control group [50.5 (48.7–52.3) minutes] (P = 0.008). Conclusions A single dose of 8 mg of dexamethasone hastened the onset and total recovery times of cisatracurium-induced block by approximately 15 and 9%, respectively if administered 2–3 h prior to surgery.

Mega Acer Kit® is more effective for warming the intravenous fluid than Ranger™ and ThermoSens® at 440 ml/h of infusion rate: an experimental performance study

Background Few studies have investigated the effectiveness of intravenous fluid warmers at low and moderate flow rates below 1,000 ml/h. In this study, we compared the effectiveness of three different fluid warmers at a low flow rate (440 ml/h). Methods We experimentally investigated the fluid warming performances of Mega Acer Kit® (Group M, n = 10), Ranger™ (Group R, n = 10), and ThermoSens® (Group T, n = 10) at 440 ml/h for 60 min. All devices were set at a warming temperature of 41℃ with preheating for 10 min. Intravenous fluids were then delivered through them. The fluid temperature (primary endpoint) was measured at 76 cm from the device after infusion for 60 min. The expected decrease in mean body temperature (secondary endpoint) after 5 h infusion for a 70 kg patient (ΔMBT5) was also calculated. Results The fluid temperature (mean [95% CI]) at 76 cm from the device, 60 minutes after the infusion was higher in group M (36.01 [35.73–36.29]℃), compared to groups T (29.81 [29.38–30.24]℃) and R (29.12 [28.52–29.72]℃) (P < 0.001). The ΔMBT5 (mean [95% CI]) was significantly smaller in group M (−0.04 [−0.04 to −0.03]℃) than that in groups T (−0.27 [−0.28 to −0.29]℃; P < 0.001) and R (−0.30 [−0.32 to −0.27]℃; P < 0.001). However, none of the fluid warmers provided a constant normothermic temperature above 36.5℃. Conclusions Mega Acer Kit® was more effective in warming the intravenous fluid with the smallest expected change in the mean body temperature, compared to Ranger™ and ThermoSens®, at a flow rate of 440 ml/h.

Hydrocortisone for refractory hypotension of very low birth weight infant with patent ductus arteriosus : a case report

To the Editor: A male infant weighing 1,090 g, 28 weeks of gestation, was scheduled to take a ligation of a patent ductus arteriosus (PDA). Eight days after birth, mean arterial pressure (MAP) has fall to \30 mmHg. We started with dopamine (5–10 lg/kg/min), to maintain the blood pressure, but this was not successful. Although we did not confirm an adrenal insufficiency (AI), we decided to start medication of hydrocortisone, 3 mg/kg/day, which resulted in over 50/35 mmHg. The hydrocortisone was tapered for 3 days because MBP was maintained at[40 mmHg, and 5 lg/kg/min of dopamine was maintained until the day of surgery. At 31 days after birth, we induced anesthesia with 2 mg/kg of ketamine, 20 lg/kg of fentanyl, and 0.9 mg/kg of rocuronium without premedication. Anesthesia was maintained by a continuous infusion of ketamine (1 mg/kg/h) and intermittent rocuronium in 50% O2 with air. After ligation of a PDA, MAP was decreased to 30 mmHg by degrees which required an increase to 10 lg/kg/ min of dopamine and the addition of 5 lg/kg/min of dobutamine to maintain over 30 mmHg. An echocardiogram showed globally normal contractility without a PDA. In spite of our efforts, mean blood pressure had fallen to 24 mmHg at 6 h after ligation. The patient was commenced on intravenous hydrocortisone (3 mg/kg/day), which increased MAP to above 30 mmHg and heart rate to 172 bpm after 90 min. After 4 h, MAP was maintained over 50 mmHg and heart rate was 190 bpm. Two days after surgery, the dopamine, dobutamine, and hydrocortisone were tapered and the blood pressure was maintained until discharge. Hypotension of very low birth weight (VLBW) premature infants is a major factor of morbidity, and mortality. Inotropes such as dopamine and dobutamine are widely used to normalize blood pressure but more than 50% of hypotensive VLBW infants requiring dopamine at doses[10 mg/kg/min develop refractory hypotension (RH) that is resistant to vasopressor [1]. Hydrocortisone is beneficial in treatment of RH, but the mechanisms are not completely understood. Down-regulation of cardiovascular adrenergic receptors and the development of relative adrenal insufficiency are thought to be the factors that may explain the corticosteroid responsiveness of RH [2, 3]. Cardiovascular response to catechol amines is attenuated due to down-regulation of the cardiovascular adrenergic receptors in VLBW infants with critical illness [2]. Moreover, VLBW infants have low adrenal reserves and reach a relatively adrenal insufficiency (AI) state in stressed situations [4]. Watterberg et al. [5] has reported hydrocortisone (1 mg/kg every 8 h) was effective for VLBW infants with AI. In this case, the infant had RH in spite of the treatment with inotropes after birth and PDA ligation, and we successfully treated him with hydrocortisone. Thus, we recommend that early hydrocortisone therapy be administered to VLBW premature infants for perioperative RH resistant to inotropes..