Consistently low levels of histidine-rich glycoprotein as a new prognostic biomarker for sepsis: A multicenter prospective observational study.

BACKGROUND: Few sepsis biomarkers accurately predict severity and mortality. Previously, we had reported that first-day histidine-rich glycoprotein (HRG) levels were significantly lower in patients with sepsis and were associated with mortality. Since the time trends of HRG are unknown, this study focused on the time course of HRG in patients with sepsis and evaluated the differences between survivors and non-survivors. METHODS: A multicenter prospective observational study was conducted involving 200 patients with sepsis in 16 Japanese hospitals. Blood samples were collected on days 1, 3, 5, and 7, and 28-day mortality was used for survival analysis. Plasma HRG levels were determined using a modified quantitative sandwich enzyme-linked immunosorbent assay. RESULTS: First-day HRG levels in non-survivors were significantly lower than those in survivors (mean, 15.7 [95% confidence interval (CI), 13.4-18.1] vs 20.7 [19.5-21.9] µg/mL; P = 0.006). Although there was no time × survivors/non-survivors interaction in the time courses of HRG (P = 0.34), the main effect of generalized linear mixed models was significant (P < 0.001). In a univariate Cox proportional hazards model with each variable as a time-dependent covariate, higher HRG levels were significantly associated with a lower risk of mortality (hazard ratio, 0.85 [95% CI, 0.78-0.92]; P < 0.001). Furthermore, presepsin levels (P = 0.02) and Sequential Organ Function Assessment scores (P < 0.001) were significantly associated with mortality. Harrell's C-index values for the 28-day mortality effect of HRG, presepsin, procalcitonin, and C-reactive protein were 0.72, 0.70, 0.63, and 0.59, respectively. CONCLUSIONS: HRG levels in non-survivors were consistently lower than those in survivors during the first seven days of sepsis. Repeatedly measured HRG levels were significantly associated with mortality. Furthermore, the predictive power of HRG for mortality may be superior to that of other singular biomarkers, including presepsin, procalcitonin, and C-reactive protein.

Histidine-rich glycoprotein as a novel predictive biomarker of postoperative complications in intensive care unit patients: a prospective observational study.

BACKGROUND: Decrease in histidine-rich glycoprotein (HRG) was reported as a cause of dysregulation of the coagulation-fibrinolysis and immune systems, leading to multi-organ failure, and it may be a biomarker for sepsis, ventilator-associated pneumonia, preeclampsia, and coronavirus disease 2019. However, the usefulness of HRG in perioperative management remains unclear. This study aimed to assess the usefulness of HRG as a biomarker for predicting postoperative complications. METHODS: This was a single-center, prospective, observational study of 150 adult patients who were admitted to the intensive care unit after surgery. Postoperative complications were defined as those having a grade II or higher in the Clavien-Dindo classification, occurring within 7 days after surgery. The primary outcome was HRG levels in the patients with and without postoperative complications. The secondary outcome was the ability of HRG, white blood cell, C-reactive protein, procalcitonin, and presepsin to predict postoperative complications. Data are presented as number and median (interquartile range). RESULTS: The incidence of postoperative complications was 40%. The HRG levels on postoperative day 1 were significantly lower in patients who developed postoperative complications (n = 60; 21.50 [18.12-25.74] µg/mL) than in those who did not develop postoperative complications (n = 90; 25.46 [21.05-31.63] µg/mL). The Harrell C-index scores for postoperative complications were HRG, 0.65; white blood cell, 0.50; C-reactive protein, 0.59; procalcitonin, 0.73; and presepsin, 0.73. HRG was independent predictor of postoperative complications when adjusted for age, the presence of preoperative cardiovascular comorbidities, American Society of Anesthesiologists Physical Status Classification, operative time, and the volume of intraoperative bleeding (adjusted hazard ratio = 0.94; 95% confidence interval, 0.90-0.99). CONCLUSIONS: The HRG levels on postoperative day 1 could predict postoperative complications. Hence, HRG may be a useful biomarker for predicting postoperative complications.

Histidine-rich glycoprotein as a prognostic biomarker for sepsis.

Various biomarkers have been proposed for sepsis; however, only a few become the standard. We previously reported that plasma histidine-rich glycoprotein (HRG) levels decreased in septic mice, and supplemental infusion of HRG improved survival in mice model of sepsis. Moreover, our previous clinical study demonstrated that HRG levels in septic patients were lower than those in noninfective systemic inflammatory response syndrome patients, and it could be a biomarker for sepsis. In this study, we focused on septic patients and assessed the differences in HRG levels between the non-survivors and survivors. We studied ICU patients newly diagnosed with sepsis. Blood samples were collected within 24 h of ICU admission, and HRG levels were determined using an enzyme-linked immunosorbent assay. Ninety-nine septic patients from 11 institutes in Japan were included. HRG levels were significantly lower in non-survivors (n = 16) than in survivors (n = 83) (median, 15.1 [interquartile ranges, 12.7-16.6] vs. 30.6 [22.1-39.6] µg/ml; p < 0.01). Survival analysis revealed that HRG levels were associated with mortality (hazard ratio 0.79, p < 0.01), and the Harrell C-index (predictive power) for HRG was 0.90. These results suggested that HRG could be a novel prognostic biomarker for sepsis.

[Anesthesia in a Patient with Giant Goiter in Whom Tracheotomy Was Performed with Standby of Percutaneous Cardiopulmonary Support].

In a 53-year-old female patient total thyroidectomy for a giant goiter under general anesthesia was scheduled. On talking, airway stenosis sounds were heard. Cervical to thoracic CT revealed left and right lobe tumors measuring 5.3 x 5.6 x 10.0 and 9.1 x 8.6 x 10.0 cm, respectively. The trachea showed stenosis at a site 3.8 to 6.5 cm below the glottis, and the narrowest lumen diameter was 3.1 mm. Due to marked tracheal stenosis, awake intubation was not selected. To maintain the airway, tracheotomy was performed under local anesthesia. Considering the risk of difficulty in ventilation during tracheostomy, 4 Fr catheter sheaths were inserted into the right femoral artery and vein for percutaneous cardiopulmonary support (PCPS). Subsequently, tracheotomy was conducted in an area peripheral to the site of stenosis. After tracheotomy, general anesthesia was started. During general anesthesia, there were no problems regarding ventilation. The tracheal cannula was removed 7 days after surgery, and the patient was discharged after 14 days. For general anesthesia in patients with giant goiter, it is important to select an airway management method in consideration of tumor-related compression of the trachea. Airway management by tracheotomy under local anesthesia with standby of PCPS may be a treatment option.

[Perioperative Management of Emergency Operation for a Patient with Carcinoid Syndrome].

We report a case of carcinoid syndrome requiring an emergency operation for an upper gastrointestinal perforation. A 46-year-old man had undergone left lower lobectomy for a lung carcinoid tumor seven years previously, and liver metastasis was found five years previously. He developed cutaneous flushing and watery diarrhea, and was diagnosed with carcinoid syndrome one year previously. Although he was treated with octreotid, his symptoms became worse and he was admitted to our hospital. During the hospital stay, he underwent an emergency operation for an upper gastrointestinal perforation. Before the operation, hemodynamics were unstable. Anesthesia was induced with sevoflurane and propofol, and maintained with sevoflurane and remifentanil. Only vasopressin was used for the treatment of hypotension. Landiolol was used for perioperative tachyarrythmia. During anesthesia, there was no severe hypotension or hypertension. After the operation, he was managed with intubation in the ICU. Octreotid was administered again for the carcinoid syndrome. Vasopressin was necessary for the treatment of hypotension in the ICU. After improvement of hemodynamics, extubation was performed on the 3rd ICU day and he was discharged from the ICU on the 4th ICU day. In conclusion, we were able to perform good perioperative management of carcinoid syndrome accompanied by hemodynamic instability.

[Two cases of general anesthesia after recovery from ARDS].

There are few reports on general anesthesia in survivors of ARDS. Patients after recovery from ARDS are at risk for compromised pulmonary function, neuromuscular weakness and cognitive dysfunction. We report 2 cases of general anesthesia in survivors of ARDS. In Case 1, a 64-year-old man who had recovered from ARDS associated with Legionella pneumonia underwent carotid endarterectomy. In Case 2, a 69-year-old man who had recovered from ARDS associated with pneumococcal pneumonia underwent hepatectomy. Concerning the preoperative assessments, the spirometry data were almost normal but Hugh-Jones classification scale was II in both cases. Diffusion disturbance might be the cause of discrepancies between good respiratory functions and limited daily activities. In both cases, anesthesia was given with propofol, fentanyl remifentanil and sevoflurane. Peak airway pressure was maintained below 15 cmH2O with pressure control ventilation. They were extubated at the end of surgery and there were no serious complications during the perioperative period.

[General anesthesia for lung resection in 7 patients with forced expiratory volume in 1 second of less than 1l].

Preoperative forced expiratory volume in 1 second less than 1 l is a risk factor for anesthesia. We report perioperative management and prognosis of 7 patients with restricted lung function who underwent lung resection under general anesthesia. We assessed the patients preoperatively from the point of view of heart-lung functions such as predicted postoperative forced expiratory volume in 1 second greater than 0.8 l, an ability of walking on the level for more than 5 minutes at his own speed without a rest, presence of hypercapnia, and degree of pulmonary hypertension. One patient was extubated on the first postoperative day because of an asthmatic attack, whereas the remaining 6 patients were extubated in the operating room. Although 1 patient developed postoperative complications of lung air leakage and pneumonia, he recovered with conservative therapy. All patients were discharged without any sequela. We were able to manage high-risk patients with limited lung functions successfully during the perioperative period without serious complications.

[A case of rocuronium-induced anaphylactic shock successfully treated with sugammadex].

We report a case of a 19-year-old male with rocuronium-induced anaphylactic shock. He was scheduled for endoscopic sinus surgery for chronic sinusitis under general anesthesia. Induction of anesthesia was done with fentanyl, propofol and sevoflurane. Just after administration of rocuronium, he developed tachycardia with extended exanthema on the face, anterior chest wall and abdomen. He was difficult to ventilate manually with mask and then intubated without difficulty. The carotid arterial pulse was not palpable and adrenaline was given intermittently to maintain blood pressure. Although the systolic blood pressure increased to 80 mmHg, hemodynamics was unstable with adrenaline. Sugammadex was then given and the blood pressure became stable without adrenaline. Exanthema also disappeared gradually. He was then transferred to ICU and extubated without any sequela. The plasma beta-tryptase increased to 46 microg x l(-1) during the shock state and returned to 14.1 microg x l(-1) 8 hrs after the event. The blood hemoglobin level also increased to 21.3 g x dl(-1) during the shock state and returned to 17.2 g x dl(-1) during the recovery phase. The laboratory data showed a marked increase in vascular permeability caused by rocuronium-induced anaphylactic shock.

[ A case of general anesthesia for the removal of extra-adrenal pheochromocytoma in a patient complicated with severe hypertrophic obstructive cardiomyopathy].

We report a case of general anesthesia for the removal of pheochromocytoma in a patient complicated with severe hypertrophic obstructive cardiomyopathy. A 65-year-old woman complained of fatigability with hypertension and diabetes mellitus. She was diagnosed as an extra-adrenal peri-aortic pheochromocytoma with severe hypertrophic obstructive cardiomyopathy. The left ventricular outflow gradient (LVOG) was 199 mmHg and the serum noradrenaline level was 13,567 pg x ml(-1) (100-450). As a preoperative management, atenolol, verapamil and disopyramide were given to decrease LVOG. Then doxazosin was given to control hypertension and to increase the circulating blood volume without deteriorating the outflow tract obstruction. LVOG decreased to 50 mmHg preoperatively. Anesthesia was given with propofol, fentanyl, remifentanil and isoflurane with a continuous infusion of diltiazem. The circulating blood volume was maintained with adequate volume loading assessed by the measurement of the left ventricular end-diastolic diameter and LVOG with transesophageal echocardiography. After the removal of the tumor, continuous infusion of noradrenaline was given to maintain the blood pressure. She was extubated in the ICU. LVOG decreased to 20 mmHg with stable hemodynamics on the second postoperative day. She was discharged from the ICU without any adverse cardiac events during the perioperative period.

[Case of general anesthesia for subtotal thyroidectomy in a pregnant woman with 27th week gestation].

We report a case of general anesthesia for subtotal thyroidectomy in a pregnant woman with 27th week gestation. A 33-year-old pregnant woman was diagnosed with thyroid carcinoma. We planned subtotal thyroidectomy at 27 weeks of gestation. We gave thiamylal, fentanyl and rocuronium for induction of anesthesia. Tracheal intubation was performed. Anesthesia was maintained with sevoflurane and fentanyl. Because of tachycardia, we tilted the operating table to displace the uterus to the left. We continued monitoring fetal heart rate during the operation. The fetal heart rate remained between 130 and 150 beats x min(-1). The operation was performed with no trouble. She gave birth to a baby at 37th week gestation. We should pay attention to maternal safety, fetal toxicity including teratogenecity, fetal asphyxia and pre-term labor. We could successfully manage her anesthesia using intraoperative fetal heart rate monitoring.