Deliberate Compensated Vasoplegia-A Novel Pharmaceutical Approach for Controlling Blood Pressure During Surgery for Pheochromocytoma.

BACKGROUND: The most dreaded adverse event of pheochromocytoma surgery is operative severe blood pressure fluctuations. Preoperative protocols with alpha-blockade have achieved controversial results. No study to date evaluated the use of operative protocols in pheochromocytoma patients. Deliberated compensated vasoplegia (DCV) is a novel pharmaceutical regimen developed at our institution to decrease severe hypertensive events. The aim of this study is to compare outcomes of pheochromocytoma resection with and without DCV protocol. METHODS: A retrospective analysis of all pheochromocytoma resections between the years 2012 and 2021 was performed. Resections performed with and without DCV protocol were compared. The primary outcome measured was the incidence of severe hypertension (MAP > 150 mmHg) during surgery. Secondary outcomes included other abnormal blood pressure measurements as well as perioperative data and complications. RESULTS: A total of 41 resections were included, 21 performed under DCV protocol, and 20 without the protocol. Analysis demonstrated no significant difference in preoperative parameters including tumor size, catecholamine levels, and preoperative alpha-blockade protocol. The use of DCV protocol resulted in significant decrease in severe hypertension incidence from 1.95 ± 3.6 to 0.03 ± 0.13 events/h, p = 0.008. Application of the DCV protocol was not associated with any other adverse events. CONCLUSIONS: This study suggests that DCV anesthesia protocol significantly decreases the incidence of severe hypertensive episodes during pheochromocytoma resection. This is the first study that describes a highly effective protocol for controlling hypertension in pheochromocytoma patients.

A Retrospective Investigation of Neuraxial Anesthesia Rates for Elective Cesarean Delivery Before and During the SARS-CoV-2 Pandemic.

BACKGROUND: Our hospital used to perform cesarean delivery under general anesthesia rather than neuraxial anesthesia, mostly because of patient refusal of members of the conservative Bedouin society. According to recommendations implemented by the Israeli Obstetric Anesthesia Society, which were implemented due to the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic, we increased the rate of neuraxial anesthesia among deliveries. OBJECTIVES: To compare the rates of neuraxial anesthesia in our cesarean population before and during SARS-CoV-2 pandemic. METHODS: We included consecutive women undergoing an elective cesarean delivery from two time periods: pre-SARS-CoV-2 pandemic (15 February 2019 to 14 April 2019) and during the SARS-CoV-2 pandemic (15 February 2020 to 15 April 2020). We collected demographic data, details about cesarean delivery, and anesthesia complications. RESULTS: We included 413 parturients undergoing consecutive elective cesarean delivery identified during the study periods: 205 before the SARS-CoV-2 pandemic and 208 during SARS-CoV-2 pandemic. We found a statistically significant difference in neuraxial anesthesia rates between the groups: before the pandemic (92/205, 44.8%) and during (165/208, 79.3%; P < 0.0001). CONCLUSIONS: We demonstrated that patient and provider education about neuraxial anesthesia can increase its utilization. The addition of a trained obstetric anesthesiologist to the team may have facilitated this transition.

The effect of preoperative anxiety on phenylephrine dose during cesarean delivery: An open controlled one-arm clinical trial.

BACKGROUND: We performed an open controlled one-arm clinical trial to assess whether preoperative anxiety influences phenylephrine dosage required to maintain normotension during cesarean section under spinal anesthesia. METHODS: Ninety-four parturients undergoing elective cesarean delivery under spinal anesthesia were included. Anxiety levels were measured using a verbal numerical scale anxiety score (0-10). Phenylephrine infusion to prevent hypotension was adjusted by a standard algorithm. The primary outcome was total phenylephrine dose. Linear uni- and multivariate regressions were performed to assess the relationship between preoperative anxiety and the outcome. P < .05 was considered statistically significant. RESULTS: We found no association between preoperative anxiety and phenylephrine dosage (R2  = 0.05). Taking the number of attempts for spinal anesthesia and surgical time into account did not lead to a significant improvement of the regression model. CONCLUSION: In conclusion, we did not find a large independent effect of preoperative anxiety on phenylephrine dose required to maintain normotension in our cohort. We believe that spinal hypotension and phenylephrine dose requirement are multifactorial and anxiety is only one of the factors in this complex interaction.

[SEX DIFFERENCES IN PHYSIOLOGICAL RESPONSES TO PAIN THROUGHOUT SURGICAL PROCEDURES].

BACKGROUND: Recent research has shown that women and men respond differently to pain, and that biological mechanisms partially moderate sex-related differences in pain sensitivity. Previous pain studies regarding the relationship between pain and physiological aspects, such as brain function and hormone levels, have demonstrated gender differences. In this study we examined whether male and female autonomic reactivity patterns to pain, defined as increases in heart rate and blood pressure, differ throughout anesthetized abdominal surgical procedures. METHODS: We retrospectively reviewed 50 patients: 25 male and 25 female patients who underwent exploratory laparotomy surgeries and had intraoperative sympathetic response to surgical stimulation and were defined as patients who had an increase of 20% in heart rate or blood pressure at surgical incision. Baseline blood pressure and heart rate data, as well as blood pressure and heart rate measurements following surgical incision were gathered. Baseline data was compared to post surgical incision data, in order to evaluate whether blood pressure and heart rate change patterns differ amongst men and women. RESULTS: Demographic data between groups was analyzed according to the T - Test. Significant difference in demographic data was observed in weight. Average changes in mean, systolic diastolic blood pressure and heart rate, were analyzed according to Wilcoxon Rank Scores. No significant differences in any variable were found between the groups. CONCLUSIONS: In order to confirm our hypothesis as to whether the autonomic nerve system, such as heart rate and blood pressure reactivity, may partially moderate sexrelated differences to pain, a large prospective study with a standardized anesthesia protocol is needed.

Protection of cultured Cyprinus carpio against a lethal viral disease by an attenuated virus vaccine.

Massive mortality of koi and common carp--Cyprinus carpio species--has been observed since 1998 in many countries worldwide, resulting in severe economic losses. The cause of the disease is an as yet unclassified large DNA virus, designated carp nephritis gill necrosis virus (CNGV) or koi herpes virus (KHV). Previously, we demonstrated that the wild type CNGV lost its pathogenecity following serial transfer in cell culture, and that clones isolated from the attenuated population can be used as a prophylactic vaccine. Here, we describe the basic conditions required for proper fish immunization so that a protection protocol may be devised. We demonstrated that carps are very sensitive to the pathogenic and the attenuated viruses, and short immersion of fish in water containing the viruses is sufficient for infection. The infection of fish with the pathogenic and the attenuated viruses is temperature-restricted; fish held at the non-permissive temperature, immediately following infection, were not affected by the pathogenic virus, and were not rendered resistant to the disease. Thus, propagation of the virus in the fingerlings is a pre-requisite for immunization. In order to increase the number of random mutations in the genome of the attenuated virus, and thus, reduce the possibility of the attenuated virus reverting to pathogenic, we irradiated it and selected additional clones appropriate for vaccination. The results of our study suggest that a safe and efficient prophylactic vaccine can be developed by selecting an appropriate attenuated virus.

Description of an as yet unclassified DNA virus from diseased Cyprinus carpio species.

Numerous deaths of koi and common carp (Cyprinus carpio) were observed on many farms throughout Israel, resulting in severe financial losses. The lethal viral disease observed is highly contagious and extremely virulent, but morbidity and mortality are restricted to koi and common carp populations. Diseased fish exhibit fatigue and gasping movements in shallow water. Infected fish had interstitial nephritis and gill necrosis as well as petechial hemorrhages in the liver and other symptoms that were not consistent with viral disease, suggesting a secondary infection. Here we report the isolation of carp nephritis and gill necrosis virus (CNGV), which is the etiologic agent of this disease. The virus propagates and induces severe cytopathic effects by 5 days postinfection in fresh koi or carp fin cell cultures (KFC and CFC, respectively), but not in epithelioma papillosum cyprini cells. The virus harvested from KFC cultures induced the same clinical signs, with a mortality of 75 to 95%, upon inoculation into naive koi and common carp. Using PCR, we provide final proof that the isolated virus is indeed the etiologic agent of food and ornamental carp mortalities in fish husbandry. Electron microscopy revealed viral cores with icosahedral morphology of 100 to 110 nm that resembled herpesviruses. Electron micrographs of purified pelleted CNGV sections, together with viral sensitivities to ether and Triton X-100, suggested that it is an enveloped virus. However, the genome of the isolated virus is a double-stranded DNA (dsDNA) molecule of 270 to 290 kbp, which is larger than known herpesviruses. The viral DNA seems highly divergent and bears only small fragments (16 to 45 bp) that are similar to the genomes of several DNA viruses. Nevertheless, amino acid sequences encoded by CNGV DNA fragments bear similarities primarily to members of the Poxviridae and Herpesviridae and to other large dsDNA viruses. We suggest, therefore, that the etiologic agent of this disease may represent an as yet unclassified virus species that is endemic in C. carpio (carp).

Pathogenesis of acute viral disease induced in fish by carp interstitial nephritis and gill necrosis virus.

A lethal disease of koi and common carp (species Cyprinus carpio) has afflicted many fish farms worldwide since 1998, causing severe financial losses. Morbidity and mortality are restricted to common carp and koi and appear in spring and autumn, when water temperatures are 18 to 28 degrees C. We have isolated the virus causing the disease from sick fish, propagated it in koi fin cell culture, and shown that virus from a single clone causes lethal disease in carp and koi upon infection. Intraperitoneal virus injection or bathing the fish in virus-containing water kills 85 to 100% of the fish within 7 to 21 days. This virus is similar to the previously reported koi herpesvirus; however, it has characteristics inconsistent with the herpesvirus family, and thus we have called it carp interstitial nephritis and gill necrosis virus. We examined the pathobiology of this disease in carp by using immunohistochemistry and PCR. We found large amounts of the virus in the kidneys of sick fish and smaller amounts in liver and brain. A rapid increase in the viral load in the kidneys was detected by using both immunofluorescence and semiquantitative PCR. Histological analyses of fish at various times after infection revealed signs of interstitial nephritis as early as 2 days postinfection, which increased in severity up to 10 days postinfection. There was severe gill disease evidenced by loss of villi with accompanying inflammation in the gill rakers. Minimal focal inflammation was noted in livers and brains. This report describes the etiology and pathology of a recently described viral agent in fish.

Efficient vaccine against the virus causing a lethal disease in cultured Cyprinus carpio.

We have isolated a virus, which causes a mortal disease in cultured ornamental Koi and Common carps (Cyprinus carpio) in many countries worldwide. This unclassified virus, which causes nephritis and gill necrosis, and so has been given the name carp nephritis and gill necrosis virus (CNGV), has a morphology resembling the herpes virus, but bears a genomic DNA of ca 250-300 kbp. So far, both others and we have been unable to find CNGV-DNA sequences possessing a significant similarity to known DNA viruses. The virus induces a lethal disease when water temperature ranges between 18 and 25 degrees C (permissive temperature). In this report, we demonstrate that carps, exposed to the virus at 23 degrees C for 3-5 days and then transferred to the non-permissive temperature of 30 degrees C, became resistant to a challenged infection and their sera demonstrated a high level of virus-specific antibodies. We have isolated attenuated non-pathogenic viruses that render virus-vaccinated carps resistant to the disease. Furthermore, vaccinated fish developed high levels of antibodies against the virus. We suggest, therefore, that this attenuated virus could be used as a live vaccine for the eradication of the mortal disease afflicting Common and ornamental carp fisheries in many countries.