Vancomycin

Vancomycin

Vancomycin is a glycopeptide antibiotic medication.

Blood levels may be measured to determine the correct dose.

When taken by mouth it is poorly absorbed.

A study described the cerebrospinal fluid (CSF) exposure of vancomycin in 8 children prescribed intravenous vancomycin therapy for cerebral ventricular shunt infection. Vancomycin CSF concentrations ranged from 0.06 to 9.13 mg/L and the CSF: plasma ratio ranged from 0 to 0.66. Two of 3 children with a staphylococcal CSF infection had CSF concentrations greater than the minimal inhibitory concentration at the end of the dosing interval 1).


Cerebrospinal fluid (CSF) penetration and the pharmacokinetics of vancomycin were studied after continuous infusion (50 to 60 mg/kg of body weight/day after a loading dose of 15 mg/kg) in 13 mechanically ventilated patients hospitalized in an intensive care unit. Seven patients were treated for sensitive bacterial meningitis and the other six patients, who had a severe concomitant neurologic disease with intracranial hypertension, were treated for various infections. Vancomycin CSF penetration was significantly higher (P < 0.05) in the meningitis group (serum/CSF ratio, 48%) than in the other group (serum/CSF ratio, 18%). Vancomycin pharmacokinetic parameters did not differ from those obtained with conventional dosing. No adverse effect was observed, in particular with regard to renal function 2).


Ichinose et al. evaluated the concentration of Vancomycin in the plasma and CSF of postoperative neurosurgical patients with bacterial meningitis and evaluated the factors that affect the transferability of VCM to CSF. The concentrations of VCM in plasma (trough) and CSF were determined in eight patients (four males and four females) with bacterial meningitis who were treated with VCM using High-performance liquid chromatography. The ratio of the VCM concentrations in CSF/plasma was also calculated by estimating the blood VCM concentration at the same time as the VCM concentration in CSF was measured. The results showed that the VCM concentration in CSF was 0.9-12.7 µg/mL and the CSF/plasma VCM concentration ratio was 0.02-0.62. They examined the effect of drainage on the transferability of VCM to CSF, which showed that the VCM concentration in CSF and the CSF/plasma VCM concentration ratio were significantly higher in patients not undergoing drainage than in patients who were undergoing drainage. The CSF protein and glucose concentrations, which are diagnostic indicators of meningitis, were positively correlated with the VCM concentration in CSF and the CSF/plasma VCM concentration ratio. Thus, VCM transferability to CSF may be affected by changes in the status of the blood-brain barrier and blood-cerebrospinal fluid barrier due to drainage or meningitis 3).

Vancomycin Indications.

see Vancomycin powder.

Intraventricular Vancomycin


1)

Autmizguine J, Moran C, Gonzalez D, Capparelli EV, Smith PB, Grant GA, Benjamin DK Jr, Cohen-Wolkowiez M, Watt KM. Vancomycin cerebrospinal fluid pharmacokinetics in children with cerebral ventricular shunt infections. Pediatr Infect Dis J. 2014 Oct;33(10):e270-2. doi: 10.1097/INF.0000000000000385. PMID: 24776517; PMCID: PMC4209191.
2)

Albanèse J, Léone M, Bruguerolle B, Ayem ML, Lacarelle B, Martin C. Cerebrospinal fluid penetration and pharmacokinetics of vancomycin administered by continuous infusion to mechanically ventilated patients in an intensive care unit. Antimicrob Agents Chemother. 2000 May;44(5):1356-8. doi: 10.1128/AAC.44.5.1356-1358.2000. PMID: 10770777; PMCID: PMC89870.
3)

Ichinose N, Shinoda K, Yoshikawa G, Fukao E, Enoki Y, Taguchi K, Oda T, Tsutsumi K, Matsumoto K. Exploring the Factors Affecting the Transferability of Vancomycin to Cerebrospinal Fluid in Postoperative Neurosurgical Patients with Bacterial Meningitis. Biol Pharm Bull. 2022;45(9):1398-1402. doi: 10.1248/bpb.b22-00361. PMID: 36047211.

Sevoflurane

Sevoflurane (Ultane®)

Mildly increases CBF and ICP, and reduces CMRO2. Mild negative inotrope, cardiac output not as well maintained as with isoflurane or desflurane.

Sevoflurane is a sweet-smelling, nonflammable, highly fluorinated methyl isopropyl ether used as an inhalational anesthetic for induction and maintenance of general anesthesia. After desflurane, it is the volatile anesthetic with the fastest onset.


The general inhalation anesthetic sevoflurane can be used for the topical treatment of complicated wounds. It is applied in liquid form and may be used to irrigate the inside of cavities. Sevoflurane also exhibits in vitro antimicrobial activity. Therefore, sevoflurane may be used as an alternative to typical antibiotic or surgical treatment of complicated, localized infections.

Joys et al. from Chandigarh, used digital subtraction angiography to compare the effects of propofol and sevoflurane on the luminal diameter of cerebral vessels and on cerebral vascular mean transit time in patients with aneurysmal subarachnoid hemorrhage (aSAH).

This prospective preliminary study included adult patients with good-grade aSAH scheduled for endovascular coil embolization; patients were randomized to receive propofol or sevoflurane anesthesia during endovascular coiling. The primary outcome was the luminal diameter of 7 cerebral vessel segments measured on the diseased and nondiseased sides of the brain at 3-time points: awake, postinduction of anesthesia, and post coiling. Cerebral transit time was also measured as a surrogate for cerebral blood flow.

Eighteen patients were included in the analysis (9 per group). Baseline and intraoperative parameters were similar between the groups. Propofol increased the diameter of 1 vessel segment at postinduction and post coiling on the diseased side and in 1 segment at post coiling on the nondiseased side of the brain (P<0.05). Sevoflurane increased vessel diameter in 3 segments at postinduction and in 2 segments at post coiling on the diseased side, and in 4 segments at post coiling on the nondiseased side (P<0.05). Cerebral transit time did not change compared with baseline awake state in either group and was not different between the groups.

Sevoflurane has cerebral vasodilating properties compared with propofol in patients with good-grade aneurysmal subarachnoid hemorrhage (aSAH). However, sevoflurane affects cerebral vascular mean transit time comparably to propofol 1).

The case of a 61-year-old male patient who suffered a cranioencephalic trauma 18 years previously is presented. The patient underwent surgeries related to the trauma on numerous occasions. To date, he has suffered various recurrent epidural abscesses, which have been treated with surgical cleaning and antibiotic treatment. In the most recent episode, he presented a frontal epidural abscess 25 mm in diameter with fistulization of the skin. The patient gave written informed consent to be treated with sevoflurane irrigation, and the Pharmacy Service authorized the off-label use. Sevoflurane was applied via a catheter placed inside the cavity during weekly outpatient procedures. The procedures began 8 weeks after the clinically and radiologically verified recovery of the abscess. By avoiding surgery and the associated hospital admission, this novel alternative may prevent patient morbidity and, furthermore, may produce important economic savings.

The treatment of complicated wounds with liquid sevoflurane may be an effective and economically efficient clinical alternative for some patients 2).


1)

Joys S, Panda NB, Ahuja CK, Luthra A, Tripathi M, Mahajan S, Kaloria N, Jain C, Singh N, Regmi S, Jangra K, Chauhan R, Soni SL, Bhagat H. Comparison of Effects of Propofol and Sevoflurane on the Cerebral Vasculature Assessed by Digital Substraction Angiographic Parameters in Patients Treated for Ruptured Cerebral Aneurysm: A Preliminary Study. J Neurosurg Anesthesiol. 2022 Jan 28. doi: 10.1097/ANA.0000000000000833. Epub ahead of print. PMID: 35090162.
2)

Ferrara P, Domingo-Chiva E, Selva-Sevilla C, Campos-García J, Gerónimo-Pardo M. Irrigation with Liquid Sevoflurane and Healing of a Postoperative, Recurrent Epidural Infection: A Potential Cost-Saving Alternative. World Neurosurg. 2016 Jun;90:702.e1-5. doi: 10.1016/j.wneu.2016.02.079. Epub 2016 Feb 24. PubMed PMID: 26924116.

Animal model

Animal model

Is a living, non-human animal used during the research and investigation of human disease, for the purpose of better understanding the disease process without the added risk of harming an actual human. The animal chosen will usually meet a determined taxonomic equivalency to humans, so as to react to disease or its treatment in a way that resembles human physiology as needed. Many drugs, treatments and cures for human diseases have been developed with the use of animal models.

Animal models representing specific taxonomic groups in the research and study of developmental processes are also referred to as model organisms.

There are three main types of animal models: Homologous, Isomorphic and Predictive. Homologous animals have the same causes, symptoms and treatment options as would humans who have the same disease. Isomorphic animals share the same symptoms and treatments, only. Predictive models are similar to a particular human disease in only a couple of aspects. However, these are useful in isolating and making predictions about mechanisms of a set of disease features.

Animal Model for microvascular anastomosis.

Animal models to understand the back pain mechanism, treatment modalities, and spinal cord injury are widely researched topics worldwide. Despite the presence of several animal models on disc degeneration and Spinal Cord Injury, there is a lack of a comprehensive review.

A methodological narrative literature review was carried out for the study. A total of 1273 publications were found, out of which 763 were related to spine surgery in animals. The literature with full-text availability was selected for the review. Scale for the Assessment of Narrative Review Articles (SANRA) guidelines was used to assess the studies. Only English language publications were included which were listed on PubMed. A total of 113 studies were shortlisted (1976-2019) after internal validation scoring.

The animal models for spine surgery ranged from rodents to primates. These are used to study the mechanisms of back pain as well as spinal cord injuries. The models could either be created surgically or through various means like use of electric cautery, chemicals or trauma. Genetic spine models have also been documented in which the injuries are created by genetic alterations and knock outs. Though the dorsal approach is the most common, the literature also mentions the anterior and lateral approach for spine surgery animal experiments.

There are no single perfect animal models to represent and study human models. The selection is based on the application and the methodology. Careful selection is needed to give optimum and appropriate results 1).

Dejerine Roussy syndrome or thalamic pain syndrome is a condition developed after a thalamic stroke, a stroke causing damage to the thalamus. Ischemic strokes and hemorrhagic strokes can cause lesioning in the thalamus. The lesions, usually present in one hemisphere of the brain, most often cause an initial lack of sensation and tingling in the opposite side of the body. Weeks to months later, numbness can develop into severe and chronic pain that is not proportional to an environmental stimulus, called dysaesthesia or allodynia. As initial stroke symptoms, numbness and tingling, dissipate, an imbalance in sensation causes these later syndromes, characterizing Dejerine–Roussy syndrome. Although some treatments exist, they are often expensive, chemically based, invasive, and only treat patients for some time before they need more treatment, called “refractory treatment.” Thalamic pain syndrome is a condition developed after a thalamic stroke. Research into its underlying mechanisms and treatment options could benefit from a valid animal model. Nine different animal models have been published, but there are relatively few reports on successful reproductions of these models and so far only little advances in the understanding or the management have been made relying on these models. In general, the construct validity (similarity in underlying mechanisms) of these animal models is relatively high, although this cannot be evaluated into depth because of lack of understanding the mechanisms through which thalamic stroke can lead to thalamic pain syndrome. The face validity (symptom similarity) is relatively low, mainly because pain in these models is tested almost exclusively through evoked mechanical/thermal hypersensitivity assessed by reflexive measures and given the conflicting results with similar tests in patients with thalamic pain syndrome. The predictive validity (similarity in treatment efficacy) has not been evaluated in most models and incorporates difficulties that are specific to thalamic pain syndrome. De Vloo et al., compare the different models regarding these types of validity and discuss the robustness, reproducibility, and problems regarding the design and reporting of the articles establishing these models. They conclude with various proposals on how to improve the validity and reproducibility of thalamic pain syndrome animal models. Until further improvements are achieved, prudence is called for in interpreting results obtained through these models 2).

Kalkowski et al. combined the advantages of the demyelination model with experimental autoimmune encephalomyelitis (EAE) to provide a local autoimmune encephalomyelitis (LAE) inside the rat brain. They induced a demyelinating lesion by immunizing male Wistar rats, followed by blood-brain barrier opening protein (vascular endothelial growth factor) by stereotactic injection. They confirmed the immunization against myelin epitopes and minor neurological impairment. The histological assessment confirmed the lesion development after both 3- and 7 days post-injection. This approach was sufficient to develop a demyelinating lesion with high reproducibility and low morbidity 3).

Experimental Neurosurgery in Animal Models (Neuromethods) From Humana Press

This volume provides a full explanation and technical details to perform surgical techniques properly on small and large animal models. The first six chapters of Experimental Neurosurgery in Animal Models focus primarily on the brain, while the next six chapters concern the spinal cord in rodents. The last four chapters provide a description of operative procedures in large animals. Written for the popular Neuromethods series, chapters include the kind of detail and key implementation advice that ensures successful results in the laboratory.

Authoritative and practical, Experimental Neurosurgery in Animal Models aims to ensure successful results in the further study of this vital field.

Murine model


1)

Goel SA, Varghese V, Demir T. Animal models of spinal injury for studying back pain and SCI. J Clin Orthop Trauma. 2020;11(5):816-821. doi:10.1016/j.jcot.2020.07.004
2)

De Vloo P, Morlion B, van Loon J, Nuttin B. Animal models for central poststroke pain: a critical comprehensive review. Pain. 2017 Jan;158(1):17-29. PubMed PMID: 27992392.
3)

Kalkowski L, Golubczyk D, Kwiatkowska J, Domzalska M, Walczak P, Malysz-Cymborska I. Local autoimmune encephalomyelitis model in a rat brain with precise control over lesion placement. PLoS One. 2022 Jan 21;17(1):e0262677. doi: 10.1371/journal.pone.0262677. PMID: 35061807.
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