Moritz Kretzschmar

The Pulmonary Immune Effects of Mechanical Ventilation in Patients Undergoing Thoracic Surgery

Mechanical ventilation (MV) may induce an inflammatory alveolar response. One-lung ventilation (OLV) with tidal volumes (Vt) as used during two-lung ventilation is a suggested algorithm but may impose mechanical stress of the dependent lung and potentially aggravate alveolar mediator release. We studied whether ventilation with different Vt modifies pulmonary immune function, hemodynamics, and gas exchange. Thirty-two patients undergoing open thoracic surgery were randomized to receive either MV with Vt = 10 mL/kg (n = 16) or Vt = 5 mL/kg (n = 16) adjusted to normal Paco2 during and after OLV. Fiberoptic bronchoalveolar lavage of the ventilated lung was performed, and cells, protein, tumor necrosis factor (TNF)-&agr;, interleukin (IL)-8, soluble intercellular adhesion molecule (sICAM)-1, IL-10, and elastase were determined in the bronchoalveolar lavage. Data were analyzed by parametric or nonparametric tests, as indicated. In all patients, an increase of proinflammatory variables was found. The time courses of intra-alveolar cells, protein, albumin, IL-8, elastase, and IL-10 did not differ between the groups after OLV and postoperatively. TNF-&agr; (8.4 versus 5.0 &mgr;g/mL) and sICAM-1 (52.7 versus 27.5 &mgr;g/mL) concentrations were significantly smaller after OLV with Vt = 5 mL/kg. These results indicate that MV may induce epithelial damage and a proinflammatory response in the ventilated lung. Reduction of tidal volume during OLV may reduce alveolar concentrations of TNF-&agr; and of sICAM-1.

Multiple inert gas elimination technique by micropore membrane inlet mass spectrometry—a comparison with reference gas chromatography

The mismatching of alveolar ventilation and perfusion (VA/Q) is the major determinant of impaired gas exchange. The gold standard for measuring VA/Q distributions is based on measurements of the elimination and retention of infused inert gases. Conventional multiple inert gas elimination technique (MIGET) uses gas chromatography (GC) to measure the inert gas partial pressures, which requires tonometry of blood samples with a gas that can then be injected into the chromatograph. The method is laborious and requires meticulous care. A new technique based on micropore membrane inlet mass spectrometry (MMIMS) facilitates the handling of blood and gas samples and provides nearly real-time analysis. In this study we compared MIGET by GC and MMIMS in 10 piglets: 1) 3 with healthy lungs; 2) 4 with oleic acid injury; and 3) 3 with isolated left lower lobe ventilation. The different protocols ensured a large range of normal and abnormal VA/Q distributions. Eight inert gases (SF6, krypton, ethane, cyclopropane, desflurane, enflurane, diethyl ether, and acetone) were infused; six of these gases were measured with MMIMS, and six were measured with GC. We found close agreement of retention and excretion of the gases and the constructed VA/Q distributions between GC and MMIMS, and predicted PaO2 from both methods compared well with measured PaO2. VA/Q by GC produced more widely dispersed modes than MMIMS, explained in part by differences in the algorithms used to calculate VA/Q distributions. In conclusion, MMIMS enables faster measurement of VA/Q, is less demanding than GC, and produces comparable results.

Misoprostol as a Therapeutic Option for Trigeminal Neuralgia in Patients with Multiple Sclerosis

Dear Editor, Trigeminal neuralgia (TN) is characterized by attacks of recurring, paroxysmal, shock-like pain within the distribution of one or more branches of the trigeminal nerve [1]. About 2% of all TN patients have multiple sclerosis (MS); similarly, about 2% of all MS patients present with TN symptoms [2]. The combination of TN and MS is one of the rare, so-called “symptomatic” forms of TN. We present three cases of “therapy-resistant MS-related” TN, in which misoprostol therapy was successful. Case 1 reports of a 65-year-old female patient with a 32-year history of MS and a 4-year history of TN (V2 only). Further findings were a hemiparesis and hemiplegia lasting 1 year and a history of hypertension. She was suffering from pain attacks with a visual analog scale (VAS) of 10/10, which made eating impossible. The bouts appeared 20 times per day and lasted approximately 10 minutes. During the neurological follow-up, she received carbamazepine (CBZ) and nutrients parenterally. Increasing the doses of CBZ caused complications such as intermittent hyponatremia and hypocalcemia. She received additional administrations of 3–4 × 10 mg/day morphine subcutaneously. As the pain attacks persist, the medication was broadened to baclofen 4 × 5 mg/day, morphine retard 3 × 10 mg/day, and gabapentin at …

Effect of Bronchoconstriction-induced Ventilation–Perfusion Mismatch on Uptake and Elimination of Isoflurane and Desflurane

Background: Increasing numbers of patients with obstructive lung diseases need anesthesia for surgery. These conditions are associated with pulmonary ventilation/perfusion (VA/Q) mismatch affecting kinetics of volatile anesthetics. Pure shunt might delay uptake of less soluble anesthetic agents but other forms of VA/Q scatter have not yet been examined. Volatile anesthetics with higher blood solubility would be less affected by VA/Q mismatch. We therefore compared uptake and elimination of higher soluble isoflurane and less soluble desflurane in a piglet model. Methods: Juvenile piglets (26.7 ± 1.5 kg) received either isoflurane (n = 7) or desflurane (n = 7). Arterial and mixed venous blood samples were obtained during wash-in and wash-out of volatile anesthetics before and during bronchoconstriction by methacholine inhalation (100 &mgr;g/ml). Total uptake and elimination were calculated based on partial pressure measurements by micropore membrane inlet mass spectrometry and literature-derived partition coefficients and assumed end-expired to arterial gradients to be negligible. VA/Q distribution was assessed by the multiple inert gas elimination technique. Results: Before methacholine inhalation, isoflurane arterial partial pressures reached 90% of final plateau within 16 min and decreased to 10% after 28 min. By methacholine nebulization, arterial uptake and elimination delayed to 35 and 44 min. Desflurane needed 4 min during wash-in and 6 min during wash-out, but with bronchoconstriction 90% of both uptake and elimination was reached within 15 min. Conclusions: Inhaled methacholine induced bronchoconstriction and inhomogeneous VA/Q distribution. Solubility of inhalational anesthetics significantly influenced pharmacokinetics: higher soluble isoflurane is less affected than fairly insoluble desflurane, indicating different uptake and elimination during bronchoconstriction.

Bronchoconstriction induced by inhaled methacholine delays desflurane uptake and elimination in a piglet model

Bronchoconstriction is a hallmark of asthma and impairs gas exchange. We hypothesized that pharmacokinetics of volatile anesthetics would be affected by bronchoconstriction. Ventilation/perfusion (VA/Q) ratios and pharmacokinetics of desflurane in both healthy state and during inhalational administration of methacholine (MCh) to double peak airway pressure were studied in a piglet model. In piglets, MCh administration by inhalation (100 μg/ml, n=6) increased respiratory resistance, impaired VA/Q distribution, increased shunt, and decreased paO2 in all animals. The uptake and elimination of desflurane in arterial blood was delayed by nebulization of MCh, as determined by Micropore Membrane Inlet Mass Spectrometry (wash-in time to P50, healthy vs. inhalation: 0.5 min vs. 1.1 min, to P90: 4.0 min vs. 14.8 min). Volatile elimination was accordingly delayed. Inhaled methacholine induced severe bronchoconstriction and marked inhomogeneous VA/Q distribution in pigs, which is similar to findings in human asthma exacerbation. Furthermore, MCh-induced bronchoconstriction delayed both uptake and elimination of desflurane. These findings might be considered when administering inhalational anesthesia to asthmatic patients.

Effects of methacholine infusion on desflurane pharmacokinetics in piglets.

The data of a corresponding animal experiment demonstrates that nebulized methacholine (MCh) induced severe bronchoconstriction and significant inhomogeneous ventilation and pulmonary perfusion (V̇A/Q̇) distribution in pigs, which is similar to findings in human asthma. The inhalation of MCh induced bronchoconstriction and delayed both uptake and elimination of desflurane (Kretzschmar et al., 2015) [1]. The objective of the present data is to determine V̇A/Q̇ matching by Multiple Inert Gas Elimination Technique (MIGET) in piglets before and during methacholine- (MCh-) induced bronchoconstriction, induced by MCh infusion, and to assess the blood concentration profiles for desflurane (DES) by Micropore Membrane Inlet Mass Spectrometry (MMIMS). Healthy piglets (n=4) under general anesthesia were instrumented with arterial, central venous, and pulmonary artery lines. The airway was secured via median tracheostomy with an endotracheal tube, and animals were mechanically ventilated with intermittent positive pressure ventilation (IPPV) with a FiO2 of 0.4, tidal volume (VT)=10 ml/kg and PEEP of 5cmH2O using an open system. The determination of V.A/Q. was done by MIGET: before desflurane application and at plateau in both healthy state and during MCh infusion. Arterial blood was sampled at 0, 1, 2, 5, 10, 20, and 30 min during wash-in and washout, respectively. Bronchoconstriction was established by MCH infusion aiming at doubling the peak airway pressure, after which wash-in and washout of the anesthetic gas was repeated. Anesthesia gas concentrations were measured by MMIMS. Data were analyzed by ANOVA, paired t-test, and by nonparametric Friedman׳s test and Wilcoxon׳s matched pairs test. We measured airway pressures, pulmonary resistance, and mean paO2 as well as hemodynamic variables in all pigs before desflurane application and at plateau in both healthy state and during methacholine administration by infusion. By MIGET, fractional alveolar ventilation and pulmonary perfusion in relation to the V.A/Q. compartments, data of logSDQ̇ and logSDV̇ (the second moments describing global dispersion, i.e. heterogeneity of distribution) were estimated prior to and after MCh infusion. The uptake and elimination of desflurane was determined by MMIMS.

Thoracic anesthesia in the elderly.

Purpose of review The mean age of patients presenting for thoracic surgery is rising steadily, associated with an increased demand for thoracic surgical treatments by geriatric patients. With increasing age, physiologic changes and comorbidities have to be considered. Thoracic anesthesia for elderly patients requires greater specific knowledge. Recent findings Respiratory mechanics change progressively during aging, and the pharmacology of different drugs is also altered with increasing age. This has implications for the preoperative, intraoperative and postoperative management of elderly patients scheduled for thoracic surgery. Special focus has to be placed on preoperative evaluation, the ventilation regime and general intraoperative management. Effective postoperative pain treatment after geriatric thoracic surgery requires careful pain assessment and drug titration. Summary Considering key points of physiology and pharmacology can help to provide best possible care for the increasing number of elderly patients in thoracic surgery. Management of geriatric patients in thoracic surgery offer opportunities for anaesthetic interventions including protective ventilation, use of different anesthetics, anaesthesia monitoring, fluid management and pain therapy.

Thoracic anaesthesia 2016.

DOI:10.1097/ACO.0000000000000289 Martin H. Fischer (1879–1962), to whom many quotes in the field of medicine have been attributed, one called physiology the stepchild of medicine and concluded that this is why Cinderella often turns out the queen. When dealing with complications during ventilation, one follows established protocols and draws from vast experience. Sometimes recalling basic physiologic principals, anatomy and pharmacology can help to make decisions, which at first glance might seem counterintuitive. Arterial hypoxemia is the ultimate result of an unfavourable ventilation/perfusion (VA/Q) relationship and increasing the FiO2 is occasionally just not enough. Acute severe hypoxemia is life-threatening and has to be corrected immediately, but even less severe hypoxemia of short duration during anaesthesia and surgery has major impact on postoperative outcome. Looking atventilation ingeneral and ventilation in thoracic anaesthesia in special, remembering the physiological principals behind ventilation/ perfusion relationships can become crucial. Baumgartner and Hedenstierna (pp. 2–7) recapitulate the basics of VA/Q matching and introduce different methods to monitor and visualize VA/Q distributions in laboratory and clinical settings. They also discuss different studies looking at effects of oxygenation during resuscitation, pneumoperitoneum, capnothorax, hyperoxia and inhaled vasodilators. When replacing the diseased lung, ultimately with a lung transplant, numerous factors may influence outcome and graft failure. In times when organs are scarce and patients often have to wait too long for a suitable match, every single transplanted organ is increasingly valuable. von Dossow and Hoechter (pp. 8–13) present strategies to reduce waiting list mortality, increase organ procurement and attenuate primary graft dysfunction. These concepts are important for thoracic surgeons, intensive care physicians and – not the least – for the patients since to date there are few possibilities for long-term substitution of lung function. Surgical thymectomy is a rare procedure for an individual surgeon and probably even rarer for an individual anaesthesiologist. Unless one works at a specialized centre, more than five to 10 cases per year is a rarity. Sungur and Sentürk (pp. 14–19) draw

Pulmonary effects of remote ischemic preconditioning in a porcine model of ventilation-induced lung injury

BACKGROUND One-lung ventilation (OLV) may result in lung injury due to increased mechanical stress and tidal recruitment. As a result, a pulmonary inflammatory response is induced. The present randomized, controlled, animal experiment was undertaken to assess the effects of remote ischemic preconditioning (RIP) on diffuse alveolar damage and immune response after OLV. METHODS Fourteen piglets (26 ± 2 kg) were randomized to control (n = 7) and RIP group (n = 7). For RIP, a blood pressure cuff at hind limb was inflated up to 200 mmHg for 5 min and deflated for another 5 min, this being done four times before OLV. Mechanical ventilation settings were constant throughout the experiment: VT = 10 ml/kg, FIO2 = 0.40, PEEP = 5cmH2O. OLV was performed by left-sided bronchial blockade. Number of cells was counted from BAL fluid; cytokines were assessed by immunoassays in lung tissue and serum samples. Lung tissue samples were obtained for histological analysis and assessment of diffuse alveolar damage (DAD) score. RESULTS Hemodynamic and respiratory data were similar in both groups. Likewise, no differences in pulmonary tissue TNF-α and protein content were found, but fewer leukocytes were counted in the ventilated lung after RIP. DAD scores were high without any differences between controls and RIP. On the other hand, alveolar edema and microhemorrhage were significantly increased after RIP. CONCLUSIONS OLV results in alveolar injury, possibly enhanced by RIP. On the other hand, RIP attenuates the immunological response and decreased alveolar leukocyte recruitment in a porcine model of OLV.

Psychiatric Disorders in Complex Regional Pain Syndrome (CRPS): The Role of the Consultation-Liaison Psychiatrist

Background Complex regional pain syndrome (CRPS) is a multifactorial disorder with complex aetiology and pathogenesis. At the outpatient pain clinic of Magdeburg University Hospital, all patients, without exception, are subject to permanent psychiatric care delivered by a consultation-liaison psychiatrist. In CRPS, psychological stabilization and treatment of the neuropathic aspects are equally important. The aim of this single-center retrospective study was to determine mental/psychiatric defects impairing pain processing at the time of investigation and show the effects of treating mental disorders and neuropathic pain with the same psychotropic drugs. Method On admission, the consultation-liaison psychiatrist examined the mental state of every patient in a semistructured interview according to AMDP (working group for methods and documentation in psychiatry). Due to the model of the Department of Anaesthesiology, we are able to compare the group of CRPS patients with all other outpatients treated for pain. Results The medical treatment of psychiatric dysfunction leads to an analgesic effect. Only every second CRPS patient had an additional psychiatric diagnosis, and 15.6% were diagnosed with depressive mood disorders and show a higher prevalence of depressive symptoms than the general population and exceed the mean for all patients treated in our pain clinic. Conclusions In neuropathies, treatment of the neuropathic pain has a modulating effect on mental disorders. As CRPS patients are frequently affected by depressions, and owing to the connection between depression and suicidal tendencies, patients should be seen by a consultation-liaison psychiatrist, and nonpsychiatrists should pay special attention to this patient group.