Ki Tae Jung

Clinical Experience of Symptomatic Sacral Perineural Cyst

Tarlov or perineural cysts are nerve root cysts found most commonly at the sacral spine level arising between covering layers of the perineurium and the endoneurium near the dorsal root ganglion and are usually asymptomatic. Symptomatic sacral perineural cysts are uncommon but sometimes require surgical treatment. A 69-year-old male presented with pain in the buttock. He was diagnosed as having a sacral cyst with magnetic resonance imaging. For the nonoperative diagnosis and treatment, caudal peridurography and block were performed. After the treatment, the patients symptom was relieved. We suggest a caudal peridural block is effective in relieving pain from a sacral cyst.

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.

The Effect of Urinary Trypsin Inhibitor Against Neuropathic Pain in Rat Models

Background Nerve injury sometimes leads to chronic neuropathic pain associated with neuroinflammation in the nervous system. In the case of chronic neuropathic pain, the inflammatory and algesic mediators become predominant and result in pain hypersensitivity following nervous system damage. It is well known that urinary trypsin inhibitor (ulinastatin, UTI) has an anti-inflammatory activity. Recently, the neuroprotective action of UTI on the nervous system after ischemic injury has been reported. Thus, we evaluated the neuroprotective effect of ulinastatin in a rat model of neuropathic pain. Methods Neuropathic pain was induced with L5 spinal nerve ligation (SNL) in male Sprague-Dawley rats weighing 100-120 g. The rats were divided into 3 groups, with n = 8 in each group. The rats in the control group (group 1) were administered normal saline and those in group 2 were administered UTI (50,000 U/kg) intravenously through the tail vein for 3 days from the day of SNL. Rats in group 3 were administered UTI (50,000 U/kg) intravenously from the 5th day after SNL. The paw withdrawal threshold was measured using the von Frey test for 3 days starting from the 5th day after SNL. Results The paw withdrawal thresholds were significantly increased in the rats of group 2 compared to the other groups (P < 0.05). Conclusions Ulinastatin, which was administered for 3 days after SNL, increased the paw withdrawal threshold and it could have a neuroprotective effect in the rat model of neuropathic pain.

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.

Curcumin, COX-2, and Protein p300/CBP

Recently, curcumin has received great interest for its emerging role in pain modulation and management [1]. Its anti-nociceptive mechanism is not clear; however, it is part of numerous mechanisms involved in CX3CR1 expression, Mu and Delta opioid receptors, 5-HT (1A) receptors, TNF-α, etc [1]. Recently, I read a report on curcumin which attenuated the pain behavior and serum COX-2 concentration in a rat model of neuropathic pain [2]. That report was of great interest. I have some additional comments about that study. First, you explained that the decreased COX-2 level after curcumin treatment is associated with the down regulation of the expression of the NF-κB-regulated gene products such as COX-2 [3]. However, interaction of the RelA subunit of NF-κB with the general co-activator protein p300/CBP is vital for RelA-dependent gene transcription [4]. Moreover, disruption of this interaction deregulates the NF-κB pathway by interfering with its negative feedback loop. Another recent study also showed that treatment with 60 mg/kg of curcumin increased the mechanical threshold, as in your study, and reduced COX-2 gene expression [5]. That study revealed that curcumin treatment downregulated the recruitment and altered the binding of protein p300/CBP at the BDNF and COX-2 promoters. Curcumin seems to alleviate neuropathic pain by inhibiting p300/CBP which acts as a vital co-activator of NF-κB instead of direct down regulation of the expression of NF-κB. Second, curcumin was used 24 hours before making the CCI model and was continued daily to day 7 post-ligation. However, in a clinical situation, neuropathic pain cannot be easily expected and usually treatment starts after neuropathic pain has developed. Thus, further studies on curcumin as a therapy for neuropathic pain is necessary for application in clinical settings.

Effects of Palonosetron, a 5-HT3 Receptor Antagonist, on Mechanical Allodynia in a Rat Model of Postoperative Pain

Background 5-hydroxytryptamine 3 (5-HT3) receptors have been known to be associated with the modulation of nociceptive transmission. However, it is uncertain whether 5-HT3 plays a role in the antinociceptive or pronociceptive pathway for incisional pain. In this study, we evaluated the effects of palonosetron, a 5-HT3 receptor antagonist, on incisional pain in rats when administered intrathecally or intraplantarly. Methods An intrathecal catheter was implanted through the cisterna magna and placed in the intrathecal space of rats. An incision in the plantaris muscle of the right hind paw was done under anesthesia with sevoflurane. Withdrawal thresholds were evaluated with the von Frey filament after 2 hours. Palonosetron (0.5 and 0.1 µg intrathecally; 0.5 µg intraplantarly) was administered and the thresholds were observed for 4 hours. Results Mechanical hypersensitivity developed after the incision. Intrathecal palonosetron (0.5 µg and 0.1 µg) did not alter the paw withdrawal threshold. Intraplantar palonosetron (0.5 µg) also did not change the paw withdrawal threshold. Conclusions Intrathecal and intraplantar palonosetron (0.5 µg) had no effect on modulating the mechanical hypersensitivity in the incisional pain model of rats.

Urinary trypsin inhibitor attenuates the development of neuropathic pain following spinal nerve ligation.

Following nerve injury, inflammatory and algesic mediators are released. This neuroinflammatory outbreak causes neuronal damage and chronic neuropathic pain. Urinary trypsin inhibitor (ulinastatin, UTI), which has anti-inflammatory properties and neuroprotective effects, is used to lower the levels of inflammatory factors during surgery. This study evaluated the effect of ulinastatin in a rat model of spinal nerve ligation (SNL). Neuropathic pain was induced by L5 and L6 SNL in male Sprague-Dawley rats. Rats were divided into three groups: group N (control) received normal saline through the tail vein for three days immediately following SNL, group U pre received ulinastatin (50,000 U/kg) intravenously for three days immediately following SNL, and group U post received ulinastatin (50,000 U/kg) intravenously for three days from the 3rd day following SNL. The paw withdrawal threshold was examined and the development of mechanical allodynia was confirmed with a behavioral test using a von Frey filament three days following SNL. On the 3rd, 5th, 7th, 14th, and 28th day following SNL, the paw withdrawal threshold was examined and the levels of inflammatory mediators (i.e., tumor necrosis factor alpha [TNF-α], interleukin-1β [IL-1β], and interleukin-6 [IL-6]) were measured by ELISA. The paw withdrawal threshold was significantly increased in the rats from group U pre compared with the rats from groups N and U post until the 7th post-SNL day (P<0.05). The levels of IL-6 also were significantly decreased in the rats from group U pre compared with the rats from group N and U post until the 7th post-SNL day (P<0.05). Ulinastatin increased the paw withdrawal threshold following SNL when it was administered before the development of neuropathic pain, and may attenuate the development of neuropathic pain.

Position does not affect the optic nerve sheath diameter during laparoscopy

Background Increase in intracranial pressure (ICP) is one of the physiologic changes during laparoscopic surgery, which is known to be associated with positional changes. Changes of ICP can be measured directly by invasive method, but ultrasonographic measurement of optic nerve sheath diameter (ONSD) is known to be a rapidly applicable technique for evaluating ICP. The aim of this study is to investigate the change of ONSD according to the positional change during laparoscopic surgery. Methods Female patients scheduled to undergo laparoscopic surgery were enrolled. Fifty-seven patients were assigned according to the position during surgery (Group T: gynecological surgery, Trendelenburg position, n = 27 vs. Group RT: laparoscopic cholecystectomy, Reverse trendelenburg position, n = 30). After induction of anesthesia, ONSD, PaCO2, end-tidal carbon dioxide (ETCO2), and mean arterial pressure (MAP) were measured. Parameters were measured at 6 time points during surgery. Results There were no significant differences in the demographic data of patients, procedure time, and anesthesia. After pneumoperitoneum and positional change, ONSD, ETCO2, and MAP increased in both groups until 15 min and returned to the baseline. However, no significant differences in changes of ONSD, PaCO2, ETCO2, and MAP were observed between two groups. Conclusions ONSD during laparoscopic surgery with pneumoperitoneum increased slightly until 15 minutes, but there were no significant differences according to the position. Increases in ICP during laparoscopic surgery with short period of pneumoperitoneum would be small in disregard of position in patients without intracranial pathology.

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.