The rule regulating pH changes during crystalloid infusion.

PURPOSE: To define the rule according to which crystalloid solutions characterized by different strong ion difference (SID) modify the acid-base variables of human plasma. METHODS: With a previously validated software, we computed the effects of diluting human plasma with crystalloid solutions ([SID] 0-60, 10 mEq/l stepwise). An equation was derived to compute the diluent [SID] required to maintain the baseline pH unchanged, at constant PCO2 and at every dilution fraction. The results were experimentally tested using fresh frozen plasma, re-warmed at 37°C, equilibrated at PCO2 35 and 78 mmHg, at baseline and after the infusion of crystalloid solutions with 0, 12, 24, 36, 48 mEq/l [SID]. RESULTS: The mathematical analysis showed that the diluent [SID] required to maintain unmodified the baseline pH equals the baseline bicarbonate concentration, [HCO3⁻], assuming constant PCO2 throughout the process. The experimental data confirmed the theoretical analysis. In fact, at the baseline [HCO3⁻] of 18.3 ± 0.3 mmol/l (PCO2 35 mmHg) the pH was 7.332 ± 0.004 and remained 7.333 ± 0.003 when the diluting [SID] was 18.5 ± 0.0 mEq/l. At baseline [HCO3⁻] of 19.5 ± 0.3 mmol/l (PCO2 78 mmHg) the pH was 7.010 ± 0.003 and remained 7.004 ± 0.003 when the diluting [SID] was 19.1 ± 0.1 mEq/l. At both PCO2 values infusion with [SID] lower or greater than baseline [HCO3⁻] led pH to decrease or increase, respectively. CONCLUSIONS: The baseline [HCO3⁻] dictates the pH response to crystalloid infusion. If a crystalloid [SID] equals baseline [HCO3⁻], pH remains unchanged at constant PCO2, whereas it increases or decreases if the [SID] is greater or lower, respectively.

Prone positioning improves survival in severe ARDS: a pathophysiologic review and individual patient meta-analysis.

Prone positioning has been used for over 30 years in the management of patients with acute respiratory distress syndrome (ARDS). This maneuver has consistently proven capable of improving oxygenation in patients with acute respiratory failure. Several mechanisms can explain this observation, including possible intervening net recruitment and more homogeneously distributed alveolar inflation. It is also progressively becoming clear that prone positioning may reduce the nonphysiological stress and strain associated with mechanical ventilation, thus decreasing the risk of ventilator-induced lung injury, which is known to adversely impact patient survival. The available randomized clinical trials, however, have failed to demonstrate that prone positioning improves the outcomes of patients with ARDS overall. In contrast, the individual patient meta-analysis of the four major clinical trials available clearly shows that with prone positioning, the absolute mortality of severely hypoxemic ARDS patients may be reduced by approximately 10%. On the other hand, all data suggest that long-term prone positioning may expose patients with less severe ARDS to unnecessary complications.

Time course of endogenous nitric oxide inhibitors in severe sepsis in humans.

AIM: Asymmetric and symmetric dimethylarginines (ADMA and SDMA, respectively) are protein breakdown markers; both compete with arginine for cellular transport and both are excreted in urine. Moreover, ADMA is a non-selective inhibitor of nitric oxide (NO) synthase that is metabolized by a specific hydrolase in which the activity during stress remains controversial. While an increase in ADMA is known to be associated with adverse events, little is known about SDMA. We investigated plasma ADMA and SDMA levels during ICU stay to reveal the time course of endogenous NO inhibition in patients with sepsis. METHODS: A post hoc analysis from a prospective random controlled trial conducted in three ICUs was performed to study the pathophysiological pathways of sepsis. ADMA, SDMA, the ratio of ADMA/SDMA (a marker of ADMA catabolism), arginine, interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and C reactive protein (CRP) were measured on days 1, 3, 6, 9, 12 and at discharge in 72 consecutive severely septic patients. RESULTS: Fasting basal glycemia, creatinine, IL-6, TNF-alpha, CRP, ADMA, and SDMA were higher than normal. The ADMA/SDMA ratio was decreased by 50%, and arginine levels were low. ADMA levels were related to the total Sequential Organ Failure Assessment (SOFA) scores and arginine levels, and inversely related to IL-6 and CRP levels. SDMA levels were related to Simplified Acute Physiologic Scores II (SAPS II), SOFA scores, blood urea, creatinine, and arginine levels. The ADMA/SDMA ratio was inversely related to IL-6 levels. In 58 ICU survivors, creatinine, IL-6, and CRP levels decreased over time; ADMA levels increased, SDMA levels remained stable, and the ADMA/SDMA ratio increased. In 14 non-survivors, creatinine, IL-6, TNF-alpha, CRP, and ADMA levels were stable, whereas the SDMA levels increased and the ADMA/SDMA ratio remained low. In both ICU survivors and non-survivors, the levels on the last ICU day confirmed the data trends. SDMA, but not ADMA, was associated with ICU mortality. CONCLUSION: ADMA catabolism appears to be activated by inflammation; its increase during the advanced septic phase in surviving patients may suggest an endogenous inhibition of NO synthesis during the full-blown septic phase. In severe sepsis, SDMA, but not ADMA, appears to be a marker of alterations in vital functions and mortality.

Dilutional acidosis: where do the protons come from?

PURPOSE: To investigate the mechanism of acidosis developing after saline infusion (dilutional acidosis or hyperchloremic acidosis). METHODS: We simulated normal extracellular fluid dilution by infusing distilled water, normal saline and lactated Ringer's solution. Simulations were performed either in a closed system or in a system open to alveolar gases using software based on the standard laws of mass action and mass conservation. In vitro experiments diluting human plasma were performed to validate the model. RESULTS: In our computerized model with constant pKs, diluting extracellular fluid modeled as a closed system with distilled water, normal saline or lactated Ringer's solution is not associated with any pH modification, since all its determinants (strong ion difference, CO(2) content and weak acid concentration) decrease at the same degree, maintaining their relative proportions unchanged. Experimental data confirmed the simulation results for normal saline and lactated Ringer's solution, whereas distilled water dilution caused pH to increase. This is due to the increase of carbonic pK induced by the dramatic decrease of ionic strength. Acidosis developed only when the system was open to gases due to the increased CO(2) content, both in its dissociated (bicarbonate) and undissociated form (dissolved CO(2)). CONCLUSIONS: The increase in proton concentration observed after dilution of the extracellular system derives from the reaction of CO(2) hydration, which occurs only when the system is open to the gases. Both Stewart's approach and the traditional approach may account for these results.

Effects of recombinant human activated protein C on the fibrinolytic system of patients undergoing conventional or tight glycemic control.

AIM: Recombinant human activated protein C (rh-APC) and tight glycemic control (TGC) have been shown to reduce mortality in septic patients. Both interventions can reduce the plasma concentration and/or activity of the most powerful suppressor of fibrinolysis, plasminogen activator inhibitor-1 (PAI-1). Our aim was to evaluate the effects on the fibrinolytic system after the administration of rh-APC in septic patients undergoing conventional or TGC. METHODS: Posthoc analysis of data was collected from 90 patients with severe sepsis/septic shock, randomized to either conventional or TGC groups. Independent of these treatments, patients with at least two organ dysfunctions simultaneously received rh-APC. Plasma levels of multiple biochemical markers for fibrinolysis, coagulation, and inflammation were determined every day for the 1st week and then on study days 9, 11, 13, 18, 23, and 28. Clinical data and sepsis-related organ failure assessment (SOFA) scores were also recorded. RESULTS: Patients who had received rh-APC exhibited significantly more impairments in fibrinolysis at baseline (PAI-1 activity 49.76 [24.61-71.82] vs 21.92 [6.47-55-83] IU/mL, P=0.03). The reductions in plasma PAI-1 activity over time associated with rh-APC treatment were different according to whether the treatment was administered to patients undergoing conventional or TGC (P=0.01). However, the most prominent reductions were in patients undergoing conventional glycemic control. Significant interactions between the two study interventions were also found for PAI-1 concentration (P<0.001), C-reactive protein (P=0.02), and interleukin-6 levels (P<0.001). CONCLUSIONS: Both rh-APC and TGC appear to improve fibrinolysis in septic patients. The reduction in the impairment of fibrinolysis associated with rh-APC treatment seems greater in patients undergoing conventional glycemic control than in those undergoing TGC.

Does recurrent laryngeal nerve anatomy condition the choice of the side for approaching the anterior cervical spine?

AIM: The anterior cervical presternocleidomastoid approach is a safe and standardized procedure. Nevertheless, in all the largest series presented in literature, a certain risk of injury to the recurrent laryngeal nerves (RLNs) is reported and the choice of the side of the approach seems to influence such risk. Our aim was to study the surgical anatomy of the RLNs and to understand whether the side of the approach can be a risk factor for their surgical damage. METHODS: We performed an anatomical dissection of 6 fresh cadavers, studying the origin and the course of both the RLNs, to assess their vulnerability in the anterior presternocleidomastoid approach to the cervical spine. RESULTS: The origin of the right RLN was at C7 in 2 cases and at T1 in 4 cases. In all cases it arose where vagus nerve crossed the subclavian artery and it was directed superiorly and transversely to the esophagotracheal groove. CONCLUSIONS: The right and left RLNs have different origin and course. Although the discussion about the best side for the anterior cervical approach is debated, in our opinion, both anatomical and surgical considerations, concerning RLNs, lead to the evidences that the left side approach, when possible, should be preferred below the level of C4.

Ghost lesions in patient with cerebral-isolated neurosarcoidosis. A case report.

We present a case of isolated cerebral neurosarcoidosis with remitting nodular lesions resembling intraventricular neoplasms. The patient, admitted at our Department for surgical treatment of a magnetic resonance imaging (MRI) demonstrated fourth ventricle lesion, presented acute intracranial hypertension. A second MRI performed before the scheduled operation showed the disappearance of the fourth ventricle lesion and a tetra-ventricular hydrocephalus. The patient has been treated with a third-ventriculostomy, followed, after 15 days, by ventriculoperitoneal shunt. High doses of steroids have been administered. Cerebrospinal fluid analysis has been conducted and a high concentration of ACE, specific marker of neurosarcoidosis, has been found. No biopsy was performed to avoid surgical complications. A systemic chemotherapy with azathioprine has been started, but the patient died six months later for worsening of the clinical conditions. The autopsy confirmed the diagnosis of neurosarcoidosis. This is the first MRI documented case of neurosarcoidosis with remitting lesions. Diagnosis of isolated neurosarcoidosis is difficult and it is based on clinical and radiological exclusion of other entities. CSF examination is useful for diagnosis, for the reported specificity and sensibility of ACE. Medical treatment is based on corticosteroids and chemotherapic agents. Neurosurgical intervention can be related to treat hydrocephalus due to ependymal and arachnoidal involvement or to remove large lesions. In our opinion biopsy should be limited only to ACE negative patients and to those who do not respond to chemotherapy.

The use of working memory for task prediction: what benefits accrue from different types of foreknowledge?

The assumption that the deployment of executive processes invariably improves task performance is implicit to cognitive theory. In particular, working memory can be used to retain and update historical information about predictable trial sequences (foreknowledge) so that subjects can anticipate and prepare for the upcoming trial more effectively. We review the effects of different types of foreknowledge on response accuracy and latency, particularly in relation to experiments investigating saccadic eye movements in humans. While it is possible to make all aspects of an impending trial predictable, varying the predictability of different components of the trial independently can reveal which cognitive operations are potentially modifiable by foreknowledge. These operations include stimulus processing, retrieval of task-set rules, and response preparation, among others. The available data suggest that, while response preparation can be completed and the response even executed before the stimulus appears (i.e. anticipation) when the subject possesses complete task-foreknowledge (knowing both the stimulus to appear and the response required), foreknowledge of the task-set alone does not permit advance configuration of the task-set rules. A taxonomy for foreknowledge is proposed, including foreknowledge for timing, stimulus, set, response, and task. Work on differentiating these effects in neurophysiology, neuroimaging, and neuropsychology is still in the early stages.

Surgical approaches to the cervico-thoracic junction.

The cervico-thoracic junction (CTJ) extends between the 7th cervical and the 4th thoracic vertebrae and comprehends the inferior portion of the brachial plexus and the parenchymatous, vascular and nervous structures of the upper mediastinum. The posterior surgical approaches, as the laminectomy or the arthro-pediclectomy, fail to expose the anterior spinal elements. Thus, further surgical approaches have been proposed: postero-lateral, antero-lateral (thoracotomies) and purely anterior. The aim of this study was to discuss indications, key anatomical landmarks and risks of the main surgical approaches to the CTJ. Ten fresh cadavers from the Anatomical Laboratory of the University of Nantes (France) were used for the surgical dissection of the CTJ. The postero-lateral and the antero-lateral approaches were performed in 4 cadavers each and the anterior approaches were studied in 2. The postero-lateral extrapleural approach (PLEA) permits an excellent antero-lateral exposure of the T2-T4 segment, preserving the parascapular musculature integrity. The thoracotomies allow the exposure of the antero-lateral portion of the junctional vertebrae, with the limits of the intrapleural approaches. The anterior approaches, including the presternocleidomastoid cervicotomy eventually associated to the sterno-claviculotomy, expose the anterior portion of the cervical and the upper thoracic vertebrae up to T4. We believe that the PLEA performs the greater surgical exposure with minimal risk of vasculo-nervous damage. Among the anterior approaches, the simple cervicotomy is the most indicated procedure in case of patients with certain anatomical conditions.

Radiation-induced schwannomas of the nervous system. Report of five cases and review of the literature.

Radiation therapy has important delayed effects on the central nervous system. Prominent among these effects is radiation necrosis of nervous tissue, but an oncogenic effect is also recognized. Both benign and malignant intracranial tumors can develop in irradiated fields, particularly in children. Most of these tumors are sarcomas, meningiomas or gliomas and only occasionally schwannomas. We report 5 cases of postirradiation acoustic nerve schwannoma observed in our Department.

Ethylene oxide sterilization of autologous bone flaps following decompressive craniectomy.

INTRODUCTION: In patients undergoing decompressive craniectomy, the bone flap is temporarily preserved either in the subcutaneous tissue of the patient or frozen. However, there are some drawbacks related to these methods. MATERIAL AND METHODS: In 16 patients in whom the bone flap was removed for decompressive craniectomy, the bone was firstly washed in hydrogen peroxide and then placed in hermetically-sealed bags and sterilized using ethylene oxide. The bone was repositioned after an average period of 4.3 months. RESULTS: One patient sustained an infection of the surgical wound which required permanent exclusion of the bone flap. In all the others, esthetic and functional results were good after an average follow-up of 20 months. Control CT-scan of the bone flap demonstrated preservation of its structural features with fusion of the bone margins and revitalization of the flap. On MRI a subdural space was again visible. CONCLUSIONS: Sterilization of the bone flap with ethylene oxide in patients undergoing decompressive craniectomy avoids some of the drawbacks related to the techniques currently used. The easiness, low cost, good aesthetic and functional results of this procedure make it a valid alternative to other techniques for preservation of autologous bone in decompressive craniectomies.

Progressive quadriparesis in adolescent with stenosis of the cervical spine.

INTRODUCTION: Progressive quadriparesis in adolescents suffering from cervical stenosis is a very rare entity. Only three cases have been reported in the literature. CASE REPORT: We report our own case of progressive quadriparesis in a young patient suffering from cervical stenosis, the first to be documented with pre- and postoperative magnetic resonance imaging.

Reconstruction of suboccipital craniectomy with autologous bone chips.

BACKGROUND: In patients submitted to suboccipital craniectomy in whom the bone is not repositioned, there may be a significant aesthetic defect due to lack of bone tissue, sometimes accompanied by paresthaesia and painful symptoms. METHOD: In 15 patients submitted to suboccipital craniectomy, the bone chips were repositioned during wound closure. FINDINGS: At a mean follow up of 19 months (from 6 to 36 months), 2 patients (13%) complained of mild wound discomfort or occasional local pain. Twelve patients underwent control CT-scan. In three cases (25%) the bone fragments had been partly reabsorbed whereas in the other 9 (75%) they either formed a thin (4 patients) or consistent (5 patients) bony wall, with variable degree of adaptation to the contour of the contralateral occipital bone. The best cosmetic and functional results were obtained in young patients in whom the cerebellar parenchyma was well-preserved, as opposed to those in whom a CSF collection had replaced areas of cerebellar tissue. INTERPRETATION: In the majority of cases in whom an osteoplastic suboccipital craniotomy is not possible, repositioning of the bone chips from suboccipital craniectomy is able to restore a bone table, thus allowing morphological and functional recovery of the occipital region.

Surgical approaches to tumours of the lateral ventricles in the dominant hemisphere.

BACKGROUND: Intraventricular neoplasms are rare tumours (1% of the tumours of the central nervous system). The surgical approach sometimes is quite difficult, particularly in the dominant hemisphere. The best choice of surgical approach is discussed. METHODS: The authors describe a series of 25 patients who underwent surgical treatment for tumours situated in the lateral ventricles of the dominant hemisphere. They discuss the most influential factors in the choice of surgical approach, which must allow maximum exposure of the lesion and vascular feeding branches without damaging highly functional areas (motor, visual and language areas). In particular, they report their experience using a low transtemporal route, between the middle and inferior gyri, for removing tumours localized in the temporal horn and/or trigone which made it possible to keep postoperative visual and phasic deficits to a minimum. RESULTS: In 5 patients the approach was transfrontal, in 10 temporal, in 6 superior parieto-occipital and in 4 transcallosal. Three patients died. Only 5 patients presented permanent deficits (anomia, apraxia and visual fields alterations). CONCLUSIONS: The size, site, hemisphere and vascularization of intraventricular tumours influence the choice of surgical approach. The basal transtemporal approach is particularly indicated to remove tumours of the temporal horn and trigone and it seems to reduce the risk of speech disturbances and alterations of posture.

Intraparenchymal haemorrhage after evacuation of chronic subdural haematoma. Report of three cases and review of the literature.

Three cases of intracerebral haemorrhage following removal of a chronic subdural haematoma are reported and the literature on this topic reviewed. The possibility of an increase in cerebral blood flow following removal of CSH, makes slow, gradual decompression mandatory in all patients submitted to cranial trapanation.