Hajime Segawa

Responses of Plasma Adrenocorticotropic Hormone, Cortisol, and Cytokines during and after Upper Abdominal Surgery

There is currently accumulating evidence for bidirectional communication between the neuroendocrine and immune systems. Various cytokines have been suggested to be involved in the stimulation of stress hormone secretion during the times of infection and inflammation. To assess the possible involvement and pathophysiologic significance of cytokines in the mechanisms responsible for the perioperative stress response of the hypothalamo-pituitary-adrenal axis, we observed the changes of plasma adrenocorticotropic hormone and cortisol levels together with those of plasma endotoxin and cytokine levels. In patients undergoing pancreatoduodenectomy, perioperative stimulation of adrenocorticotropic hormone and cortisol secretion was accompanied by a significant elevation of plasma cytokine levels. Application of epidural block up to the upper thoracic levels failed to suppress this stress response effectively. In patients undergoing unilateral total hip replacement, the response of plasma hormone levels was smaller and briefer with no significant increase of plasma cytokine levels. Application of epidural block up to the lower thoracic levels suppressed this hormonal response almost completely. In patients undergoing pancreatoduodenectomy, a significant elevation of plasma endotoxin level was followed by a gradual but significant elevation of plasma tumor necrosis factor alpha and interleukin-6 levels. It seems likely that the stimulatory effects of these cytokines on the secretion of adrenocorticotropic hormone and cortisol might be involved in the development of the greater and more prolonged stress response of hypothalamo-pituitary-adrenal axis. Our present study suggests that not only neural input from the surgical wound but also stimulation of cytokine production were responsible for the development of the stress response of the hypothalamo-pituitary-adrenal axis during and after upper abdominal surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

Xenon has greater inhibitory effects on spinal dorsal horn neurons than nitrous oxide in spinal cord transected cats.

UNLABELLED Xenon (Xe) suppresses wide dynamic range neurons in cat spinal cord to a similar extent as nitrous oxide (N2O). The antinociceptive action of N2O involves the descending inhibitory system. To clarify whether the descending inhibitory system is also involved in the antinociceptive action of Xe, we compared the effects of Xe on the spinal cord dorsal horn neurons with those of N2O in spinal cord-transected cats anesthetized with alpha-chloralose and urethane. We investigated the change of wide dynamic range neuron responses to touch and pinch by both anesthetics. Seventy percent Xe significantly suppressed both touch- and pinch-evoked responses in all 12 neurons. In contrast, 70% N2O did not show significant suppression in touch- and pinch-evoked responses. These results suggest that the antinociceptive action of Xe might not be mediated by the descending inhibitory system, but instead may be produced by the direct effect on spinal dorsal horn neurons. IMPLICATIONS Xenon (Xe) is an inert gas with anesthetic properties. We examined the antinociceptive effects of Xe and nitrous oxide (N2O) in spinal cord-transected cats. Our studies indicate that Xe has a direct antinociceptive action on the spinal cord that is greater than that of N2O.

Isoflurane and Sevoflurane Augment Norepinephrine Responses to Surgical Noxious Stimulation in Humans

Background Suppression of hypertensive response to noxious stimulation by volatile anesthetics may be a result of suppression of the stimulation‐induced norepinephrine response or that of the cardiovascular response to catecholamines, or both. The suppression of the cardiovascular response is established, but that of norepinephrine response has not been confirmed. The authors hypothesized that the suppression of cardiovascular response but not that of norepinephrine response plays a major role in suppressing the noxious stimulation‐induced hypertensive response by volatile anesthetics. Methods Forty healthy donors for living‐related liver transplantation were allocated to four groups: receiving 1.2% (end‐tidal) isoflurane in oxygen and nitrogen, 2.0% isoflurane, 1.7% sevoflurane, or 2.8% sevoflurane. The intraoperative plasma norepinephrine and epinephrine concentrations, arterial blood pressure and pulse rate were measured for the first 15 min of surgery and were compared with the preoperative values. Results Norepinephrine and epinephrine concentrations both increased intraoperatively in all four groups. The values of maximum increase the area under the concentration‐versus‐time curve of norepinephrine were greater in the high dose groups of both anesthetics. The intraoperative blood pressure did not differ by different doses of anesthetics, and the degree of increase of blood pressure was not proportional to the plasma catecholamine concentrations. Conclusion The effects of isoflurane and sevoflurane on the surgical noxious stimulation‐induced norepinephrine response were inversely proportional to the dose. The suppression of noxious stimulation‐induced blood pressure response by anesthetics that were studied may be the result of suppression of the responses of vascular smooth muscle and myocardium to catecholamines.

The Role of the Phrenic Nerves in Stress Response in Upper Abdominal Surgery

Previous studies have failed to demonstrate a block of the endocrine response to upper abdominal surgery by thoracic epidural analgesia.To clarify the bases for this failure, we compared the effects of epidural analgesia of different dermatome levels up to C8-T2 or C3-4. The patients who received general anesthesia alone showed significant increases of adrenocorticotropic hormone (ACTH) and arginine vasopressin (AVP) immediately after skin incision. The patients with C8-T2 blocked developed significant increases in these hormones, not after the skin incision, but after the intraabdominal procedure. Of the eight patients with C3-4 block, six developed no such responses throughout the study period. The responses of oxytocin (OXT) and prolactin (PRL) were more susceptible to epidural analgesia and were blocked at the C8-T2 level. Growth hormone (GH) showed no correlation with surgical procedures and epidural block. These findings indicate that the nociceptive neural information during upper abdominal surgery is conveyed by the sensory fibers included in both the thoracic and lumbar spinal nerves that innervate the abdominal wall and the intraabdominal viscera, and by the phrenic nerves that innervate the diaphragm. The rationale for postulating the involvement of the phrenic nerves can be referred to the embryonal descent of the diaphragm from the C3-5 myotomes that serves as the upper wall of the abdominal cavity. (Anesth Analg 1996;82:1215-24)

How transplant surgeons can overcome the inevitable insufficiency of allograft size during adult living-donor liver transplantation: strategy for donor safety with a smaller-size graft and excellent recipient results.

Small‐for‐size grafts are an issue in liver transplantation. Portal venous pressure (PVP) was monitored and intentionally controlled during living‐donor liver transplantation (LDLT) in 155 adult recipients. The indocyanine green elimination rate (kICG) was simultaneously measured in 16 recipients and divided by the graft weight (g) to reflect portal venous flow (PVF). The target PVP was <20 mmHg. Patients were divided by the final PVP (mmHg): Group A, PVP < 12; Group B, 12 ≤ PVP < 15; Group C, 15 ≤ PVP < 20; and Group D, PVP ≥ 20. With intentional PVP control, we performed splenectomy and collateral ligation in 80 cases, splenectomy in 39 cases, and splenectomy, collateral ligation, and additional creation in five cases. Thirty‐one cases received no modulation. Groups A and B showed good LDLT results, while Groups C and D did not. Final PVP was the most important factor for the LDLT results, and the PVP cutoffs for good outcomes and clinical courses were both 15.5 mmHg. The respective kICG/graft weight cutoffs were 3.5580 × 10−4/g and 4.0015 × 10−4/g. Intentional PVP modulation at <15 mmHg is a sure surgical strategy for small‐for‐size grafts, to establish greater donor safety with good LDLT results. The kICG/graft weight value may have potential as a parameter for optimal PVF and a predictor for LDLT results.

Thrombotic microangiopathy-like disorder after living-donor liver transplantation: a single-center experience in Japan.

AIM To investigate thrombotic microangiopathy (TMA) in liver transplantion, because TMA is an infrequent but life-threatening complication in the transplantation field. METHODS A total of 206 patients who underwent living-donor liver transplantation (LDLT) were evaluated, and the TMA-like disorder (TMALD) occurred in seven recipients. RESULTS These TMALD recipients showed poor outcomes in comparison with other 199 recipients. Although two TMALD recipients successfully recovered, the other five recipients finally died despite intensive treatments including repeated plasma exchange (PE) and re-transplantation. Histopathological analysis of liver biopsies after LDLT revealed obvious differences according to the outcomes. Qualitative analysis of antibodies against a disintegrin-like domain and metalloproteinase with thrombospondin type 1 motifs (ADAMTS-13) were negative in all patients. The fragmentation of red cells, the microhemorrhagic macules and the platelet counts were early markers for the suspicion of TMALD after LDLT. Although the absolute values of von Willebrand factor (vWF) and ADAMTS-13 did not necessarily reflect TMALD, the vWF/ADAMTS-13 ratio had a clear diagnostic value in all cases. The establishment of adequate treatments for TMALD, such as PE for ADAMTS-13 replenishment or treatments against inhibitory antibodies, must be decided according to each case. CONCLUSION The optimal induction of adequate therapies based on early recognition of TMALD by the reliable markers may confer a large advantage for TMALD after LDLT.

Regulation of interleukin-1 receptors on AtT-20 mouse pituitary tumour cells

To study the cellular mechanisms of interleukin‐I (IL‐1) in the pituitary corticotroph, we studied the properties of IL‐1 receptors on a mouse pituitary ACTH‐producing cell line, AtT‐20. Scatchard plot analysis revealed a single type of receptor with a K d (dissociation constant) of 93 pM, and 482 binding sites/cell. [125I]IL‐1α binding competed with IL‐1α and IL‐1β in an equimolar fashion. A 24 h pre‐incubation with either CRH, epinephrine or nor‐epinephrine increased the [125I]IL‐1α binding sites in the AtT‐20 cells and conversely, a similar pre‐incubation with either dexamethasone or tumour necrosis factor‐α (TNFα) decreased them without affecting the affinity of the receptors in either case.

Omission of fentanyl during sevoflurane anesthesia decreases the incidences of postoperative nausea and vomiting and accelerates postanesthesia recovery in major breast cancer surgery

PurposeOur purpose was to investigate the effect of omission of fentanyl during sevoflurane anesthesia on the incidences of postoperative nausea and vomiting and on postanesthesia recovery in female patients undergoing major breast cancer surgery.MethodsFemale patients (American Society of Anesthesiologists [ASA] physical status [PS] class I-II; age, 28–84 years) undergoing major breast cancer surgery were randomized to one of two anesthesia maintenance groups: sevoflurane-fentanyl anesthesia (SF; n = 25) or fentanyl-free sevoflurane anesthesia (S; n = 26). All patients were administered with propofol 2 mg·kg−1 intravenously for anesthesia induction, a laryngeal mask airway was placed, and they received rectal diclofenac and local infiltration anesthesia. Anesthesia was maintained with sevoflurane in oxygen-air and they breathed spontaneously. The patients in group SF received fentanyl 0.1 mg intravenously and those in group S received normal saline during anesthesia.ResultsGroup SF revealed higher incidences of postoperative nausea (68% vs 27%) and vomiting (32% vs 8%) in the first 24 postoperative hours than group S. The median (25th–75th percentile) length of time from postanesthesia care unit (PACU) admission to ambulation was significantly longer in group SF (n = 23) at 195 min (158–219 min), than in group S, at 141 min (101–175 min). Two patients in group SF could not walk during the PACU stay.ConclusionOmission of fentanyl during sevoflurane anesthesia, combined with diclofenac and local infiltration anesthesia, decreases the incidences of postoperative nausea and vomiting and accelerates postanesthesia recovery in patients undergoing major breast cancer surgery.

Use of noninvasive ventilation for pediatric patients after liver transplantation: Decrease in the need for reintubation

Noninvasive ventilation (NIV) refers to ventilation delivered through a noninvasive interface (a nasal or face mask) rather than an invasive interface (an endotracheal tube or tracheostomy). The role of NIV in preventing reintubation after abdominal surgery in pediatric patients is uncertain. Therefore, we evaluated the role of NIV for this purpose in pediatric patients after liver transplantation. We successfully started using NIV for respiratory complications (RCs) in pediatric patients undergoing liver transplantation in 1999. For this report, we screened all medical records of patients under the age of 12 years who underwent liver transplantation between 2001 and 2009, and we retrieved data for cases at high risk of extubation failure. We retrospectively compared the clinical outcomes of patients who received NIV during their intensive care unit (ICU) stay and patients who did not. Data for 94 cases (92 patients) were included in this analysis. NIV was used in 47 patients during their ICU stay. The rate of reintubation for RCs was significantly lower in NIV patients versus non‐NIV patients [3/47 (6.4%) versus 11/47 (23.4%), P = 0.02]. Furthermore, the discharge rate from the ICU was significantly better for NIV patients versus non‐NIV patients. The use of NIV after extubation prevented the worsening of atelectasis and stabilized respiratory conditions in this cohort. No major changes in operative procedures or other treatments during the examined period were found. In conclusion, NIV is acceptable and promising for the respiratory management of pediatric patients undergoing liver transplantation. Its use may stabilize respiratory conditions and decrease the need for reintubation in pediatric liver transplant patients, and it may also facilitate an early ICU discharge. Liver Transpl 18:1217–1225, 2012.

The role of CRF1 receptors for sympathetic nervous response to laparotomy in anesthetized rats

Corticotropin-releasing factor (CRF) is released in response to various types of stressors and mediates endocrine, autonomic, immune, and behavioral responses to stress through interaction with CRF1 and CRF2 receptors. To investigate the role of CRF1 receptors in physiological responses to surgical stress, we analyzed the effects of two different non-peptide selective CRF1 receptor antagonists (JTC-017 and CP-154,526) and a peptide non-selective CRF receptor antagonist (astressin) on laparotomy-induced sympathetic nervous responses in isoflurane-anesthetized rats. JTC-017, CP-154,526, and astressin similarly suppressed plasma ACTH elevation induced by laparotomy. JTC-017 and CP-154,526 significantly augmented plasma noradrenaline and adrenaline responses to laparotomy, while astressin showed no effect on these responses. Laparotomy-induced maximum increases in mean blood pressure and heart rate were augmented by JTC-017, but were not affected by astressin. The results suggested for the first time that there was a pathway to attenuate sympathetic nervous response to surgical stress through CRF1 receptors in the central nervous system.