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Current guidelines for the provision of safe anaesthesia from the World Health Organization and the World Federation of Societies of Anaesthesiologists (WFSA) are unachievable in a majority of low and middle-income countries (LMICs) worldwide. Current guidelines for anaesthesia and patient safety provisions from the WHO and WFSA are compared with local ability to achieve these recommendations in LMICs. Influential international organizations have historically published anaesthesia guidelines, but for the most part, without impacting substantial documentable changes or outcomes in low-income environments. This analysis, and subsequent recommendations, reviews the effectiveness of existing strategies for international guidelines, and proposes practical, step-wise implementation of patient safety approaches for LMICs.

In 1978, Drs. R Knill and A. Gelb published the results of a study to measure the effect of subanesthetic levels of halothane on the ability of fit volunteers to respond to sustained hypoxia, and to determine how long potentially hazardous levels of halothane persist after a brief non-complex surgical procedure in healthy patients. The purpose of this commentary is to highlight the historical context of their findings and the impact of their work on our modern day practice of anesthesia.In six fit male volunteers, steady states of halothane reduced the ventilatory response to normocapnic hypoxemia (PETO2 40 mmHg) by ~ 50% at 0.05 MAC and by 70% at 0.10 MAC without affecting resting levels of ventilation. Subjects remained easily rousable and coherent with full memory of events. Symptoms of hypoxemia were markedly reduced or totally absent during hypoxic periods. In five patients recovering from dental procedures (mean duration 59 min), 0.10 MAC halothane levels persisted in the recovery room for approximately one hour.Patients emerging from a brief (about one hour) halothane anesthetic, although appearing conscious, may have a hazardous degree of depression of the usually protective ventilatory response to hypoxemia for about one hour in the recovery room. Both the symptoms and signs of hypoxemia will be substantially reduced during this emergence phase, enhancing the risk that severe hypoxic episodes may go unrecognized.Gelb AW, Knill RL.Subanaesthetic halothane: Its effect on regulation of ventilation and relevance to the recovery room. Can Anaesth Soc J 1978; 25: 488-94.

Using a radiologic technique, the position and pattern of movement of the diaphragm have been evaluated in three adult volunteers, both awake and anesthetized, during spontaneous ventilation and with muscle paralysis and mechanical ventilation. Studies were made with the subjects in supine and left lateral decubitus positions with tidal and large-volume breaths. Positive end-expiratory pressure (PEEP) was added in studies of two subjects. During spontaneous ventilation awake or anesthetized, because of regional mechanical advantages, the dependent part of the diaphragm had the greatest displacement despite the higher intraabdominal pressure in this region. Paralysis, awake or anesthetized, caused a cephalad shift of the end-expiratory position of the diaphragm that was disproportionately large in dependent regions. It also reversed the pattern of diaphragmatic displacement. The passive diaphragm was displaced preferentially in nondependent zones where abdominal pressure is least. Consequently, PEEP could not restore the diaphragm to its awake functional residual capacity position, and large breaths also could not duplicate the pattern of displacement achieved spontaneously.

Efforts to minimize ventilator-induced lung injury in adults with hypoxemic respiratory failure have recently focused on the potential role of high-frequency oscillatory ventilation (HFOV). However, HFOV has been studied in newborns with hypoxemic respiratory failure for nearly 3 decades. In this brief review, we attempt to summarize key physiological principles learned from this cumulative neonatal/pediatric experience with HFOV.

The current challenge in neonatal ventilatory care is to select among proliferating options that include extracorporeal membrane oxygenation (ECMO), high-frequency ventilation (HFV), and partial liquid ventilation (PLV). More and more options in pressure and flow waveforms, triggering sensors, synchronization options, and breath-by-breath pressure, flow, and volume monitoring are available on conventional ventilators. All of these new options offer value over the ventilatory modes of the 1970s and 1980s that were executed without real understanding of the impact of ventilatory pattern on the evolution of the lung injury process. These novel therapies raise both the therapeutic potential and the complexity of neonatal ventilation to new levels. Such developments make it imperative that we as anesthesiologists understand the individual roles, risks, and benefits of these new approaches.

Both ventilator pattern and neutrophil activation influence lung injury in adult respiratory distress syndrome (ARDS). We therefore questioned whether ventilator pattern independently affects neutrophil accumulation and function in early ARDS. Thirty-five New Zealand White rabbits were anesthetized, paralyzed, and prepared using sterile techniques. Fifteen surfactant-depleted animals were randomized and ventilated for 4 h using high-frequency oscillatory ventilation (HFO) at 15 Hz with an inspired O2 fraction = 1.0 and arterial PO2 (PaO2) > 400 Torr (a pattern known to reverse atelectasis) or conventional mechanical ventilation (CMV) with PaO2 = 80–100 Torr (a pattern with some atelectasis despite positive end-expiratory pressure). Eight normal animals on CMV with PaO2 > 400 Torr served as a reference group (NorCMV). NorCMV animals progressively increased circulating polymorphonuclear neutrophil (PMN) numbers and had minor pressure-volume curve alterations but no other significant changes. Lavaged CMV animals developed the characteristic gas exchange and marked pressure-volume curve abnormalities of ARDS. Circulating PMNs remained constant but developed decreased chemotactic activity, whereas lung neutrophil numbers increased significantly (P = 0.0002) and had substantially enhanced chemiluminescence (P = 0.0003 vs. NorCMV animals). Although lavaged HFO animals accumulated an intermediate number of lung neutrophils (lung myeloperoxidase > NorCMV animals; P = 0.003), the chemiluminescence and chemotaxis of these PMNs were the same as in cells from NorCMV animals. We concluded that both the degree of neutrophil activation and lung injury can be minimized by preventing cyclic alveolar/airway expansion and collapse in the surfactant-deficient lung by use of appropriate ventilator patterns.

We evaluated four ventilator patterns after the administration of 80 mg/kg bovine lipid extract surfactant (LES) to anesthetized, paralyzed, saline-lavaged New Zealand white rabbits. Two ventilator types were compared: high frequency oscillatory ventilation (HFO) versus conventional mechanical ventilation (CMV), each at high (HI) and low (LO) end-expiratory lung volumes (EELV); n = 6, each group; treatment duration = 4 h. Target PaO2 ranges were > 350 mm Hg for groups with high EELV (i.e., HFO-HI and CMV-HI) and 70 to 100 mm Hg for those with low EELV (i.e., HFO-LO and CMV-LO). Ventilator pressures were limited to < or = 39/9 cm H2O in the CMV-HI group. Five of six CMV-HI-treated animals did not maintain target PaO2 levels. Both ventilator type and strategy influenced outcome significantly. Animals managed with HFO had higher mean arterial pressures (p = 0.004), lower mean airway pressures (Paw) (p < 0.00008) and HCO3- requirements (p < 0.02), larger inflation (p = 0.003) and deflation (p < 0.00001) respiratory system volumes at 10 cm inflation pressure, and higher lung lamellar body (p = 0.0006) and lavage fluid (p = 0.003) phospholipid quantities than did CMV-treated animals. The deflation P-V curve (p = 0.0004), lamellar body (p < 0.00001) and lavage fluid (p = 0.0002) phospholipid levels were superior after the high EELV strategy. We conclude that ventilator pattern strongly influences exogenous surfactant efficacy. Benefits arise from keeping EELV high enough to prevent atelectasis and using small (approximately 2 ml/kg) tidal volumes to prevent overdistension.(ABSTRACT TRUNCATED AT 250 WORDS)

The potential role of HFV has yet to be fully defined. Its use should be approached with caution, ensuring that the possible benefits outweigh new hazards. Only further rigorously controlled trials, designed to make optimum use of the special features of HFV, will furnish the information we need.

Mechanical ventilators have only two functions: to provide a flux to eliminate carbon dioxide from those who will not or cannot breathe and to establish an adequate gas-exchanging volume to reduce shunting. The concept of volume recruitment to reduce shunting goes back at least to Mead and Collier in 1959,1 who showed that without periodic inflations there was a progressive fall in compliance during prolonged mechanical ventilation. Much of the subsequent history of mechanical ventilation in acute lung disease has really been the search for better methods of volume recruitment. The lung has to be inflated past the pressure at which atelectatic lung begins to open and be maintained above its closing pressure (that pressure below which alveoli and airways start to close again).

Objective: To perform a functional evaluation of five different high-frequency, oscillatory-type ventilators that are currently being marketed for neonatal high-frequency oscillation. Design: Observational animal study. Setting: Laboratory. Subjects: New Zealand White male rabbits. Interventions: Oscillator waveforms and delivered volumes were measured plethysmographically for the following ventilators: the SensorMedics 3100 A; the Drager Baby Log 8000; the Metran Humming V; the Infant Star; and the Infant Star 950. The Independent variables which were adjusted Included frequency (5 to 15 Hz), amplitude (25% to 100%), mean airway pressure (5 to 25 cm H 2 O) and lung injury. Measurements and Main Results: At 15 Hz, the volume delivered at the 100% amplitude setting varied from 2.1 to 8.8 mL. Generally, the delivered volume decreased with increasing frequency, and with increased percentage of amplitude. Volume delivery was relatively unaffected by mean airway pressure but decreased with lung injury. Waveforms ranged from pure sinusoidal to a complex square wave. The handling of inspiration/expiration time ratios was ventilator specific. The SensorMedics inspiration/ expiration ratio is user selected over a range from 1:2.3 (30% inspiratory time) to 1 :1 (50% inspiratory time) and once selected it is consistent over its entire range of operating frequencies. The Drager ratio is machine determined and varied from 1:2.5 at 5 Hz to 1:1 at 15 Hz. Inspiratory time of the Infant Star is machine set at 18 msecs such that the inspiration/expiration ratio is 1:10.1 at 5 Hz and 1:2.7 at 15 Hz. The Humming V has a fixed inspiration/expiration ratio of 1:1. The relationship of the mean airway pressure displayed on the ventilator to the alveolar occlusion pressure varied considerably among devices. The displayed mean pressure could either overestimate (SensorMedics at 33% inspiratory time or Infant Star), approximate (Humming V), or underestimate (Drager) the mean lung distending pressure measured during a brief occlusion maneuver. Conclusions: The findings demonstrate large variations in machine performance. The ventilators also differed profoundly in complexity of operation and versatility as neonatal ventilators.

A 64-year-old man presented with gross painless hematuria.Cystoscopy revealed a submucosal bladder neck mass coveredby normal urothelium. During transurethral resection, the patientdeveloped hemodynamic crisis including sinus bradycardia.Histopathologic examination revealed a primary bladder compositeparaganglioma-ganglioneuroma (CPG). The patient underwentpartial cystectomy and is symptom-free after one year. BladderCPGs are extremely rare neoplasms that may result in lifethreateningcatecholamine secretion, especially during tumourmanipulation. These tumours require complete surgical excisionand should be included in the differential diagnosis of any solitarybladder mass covered by normal urothelium, especially whenthere is a history of hypertension or micturition attacks.

OBJECTIVES To test whether the pulmonary risk of repeated volume recruitment is greater or less than the risk associated with unreversed atelectasis during 6 hrs of high-frequency oscillatory ventilation in the atelectasis-prone rabbit lung. DESIGN Prospective, controlled, randomized comparison over 6 hrs of ventilator management. SETTING Laboratory. SUBJECTS Twenty-eight adult New Zealand white male rabbits (weight 2.3 to 2.8 kg). BACKGROUND Controversy exists over whether high-frequency oscillatory ventilation should be used with volume recruitment maneuvers in the atelectasis-prone lung, or be used at low mean and peak pressures without volume recruitment to avoid the risks of even transient pulmonary overdistention. Potential risks and benefits accompany both alternatives. INTERVENTIONS We evaluated the pulmonary effects of three high-frequency oscillatory ventilation protocols in anesthetized rabbits made surfactant deficient by saline lavage, using animals ventilated with conventional positive-pressure ventilation with positive end-expiratory pressure as a reference group; n = 5 in each group. The three high-frequency oscillatory ventilation groups were ventilated for 6 hrs at 15 Hz (900 breaths/min), FIO2 = 1.0. The repeated stretch group received 15-sec sustained inflations at 30 cm H2O mean airway pressure every 20 mins, with maintenance mean airway pressure sufficient to keep PaO2 > 350 torr (46.7 kPa). The repeated deflation group was maintained at levels that produced PaO2 70 to 120 torr (9.3 to 16 kPa), with the endotracheal tube opened to atmospheric pressure for 15 secs every 20 mins. Animals in the repeated stretch after deflations group were managed as in the repeated stretch protocol but each sustained inflation was preceded by a 15-sec deflation to functional residual capacity. The conventional positive-pressure ventilation group was ventilated at rates of 30 to 100 breaths/min, keeping PaO2 70 to 120 torr (9.3 to 16 kPa). End-points included terminal functional residual capacity and a compliance index computed from respiratory system pressure-volume curves. MEASUREMENTS AND MAIN RESULTS After 6 hrs of ventilation, respiratory system compliance in the repeated stretch group had returned to control values (1.35 +/- 0.18 [SD] mL/kg/cm H2O). Respiratory system compliance was significantly less than this number in both the repeated deflation (0.89 +/- 0.08) and repeated stretch after deflations (1.24 +/- 0.22) groups (p < .05). Respiratory system compliance after 3 hrs of conventional positive-pressure ventilation decreased to 0.34 +/- 0.10 mL/kg/cm H2O. Functional residual capacity changes paralleled these changes of respiratory system compliance. CONCLUSIONS These data demonstrate that the potential pulmonary risk of repeated lung stretch during volume recruitment is significantly less than the damage arising from the avoidance of such maneuvers in lungs in which alveolar recruitment is possible. We conclude that sustained inflations during high-frequency oscillatory ventilation produce the benefits of increased oxygenation for a given mean airway pressure plus decreased progression of lung injury.

Several indices have been introduced as convenient alternatives to calculation of the physiological shunt fraction (Qs/QT) for the assessment of pulmonary gas exchange. These include: the arterial-alveolar oxygen tension ratio (a/APO2), the arterial oxygen tension-inspired oxygen concentration ratio (PaO2/FIO2), the respiratory index (RI), [A-a)DO2/PaO2) and the alveolar-arterial oxygen tension difference [A-a)Do2). These indices are in use clinically despite the fact that they may not accurately predict gas exchange in situations where FIO2, Qs/QT or arterial-venous oxygen content is changing. The clinical stability of each of these indices, relative to the behaviour of the physiological shunt, was therefore investigated prospectively in ten mechanically ventilated postoperative adults as FIO2 was varied from 0.30 to 1.00. None of the indices studied reliably reflected the behaviour of the physiological shunt. As FIO2 was increased incrementally from 0.30 to 1.00, 42 to 55 per cent of the measured changes in these indices were opposite in direction to the corresponding changes in the physiological shunt. The maximum magnitudes of the opposite changes were substantial; 24 and 22 per cent for the a/APO2 and PaO2/FIO2 ratio respectively, 67 per cent for the RI and 101 per cent for the (A-a)DO2. We conclude that the use of any of these indices for clinical assessment of a patient's gas exchange defect when FIO2 is varying can be substantially misleading.

Summary It has been established that HFV is effective in maintaining pulmonary gas exchange in the normal lung and in a variety of pathophysiologic conditions. To date, proven rate-related advantages over conventional ventilation are few. Therefore present clinical indications are limited, and the added hazards imposed on the patient by these high-frequency techniques must always be considered. In most situations the use of HFV must still be considered to be experimental. There are, however, several areas in which HFV may add significant new treatment options to existing technology. These areas include maintenance of CO2 elimination at lower peak and mean airway pressures in cases of established barotrauma, provision of a nearly motionless operative field in circumstances in which this confers substantial benefits, treatment of hypoxia due to diffuse atelectasis, and minimization of ventilator-associated lung injury. The first two applications exploit the ability of HFV to achieve gas transport at low pressures; the latter two exploit the ability of HFV to support gas exchange at relatively high mean pressures with an acceptable rate of complications. In the latter sense, high-frequency ventilators can be viewed as a new tool that can enable us to achieve something close to CPAP in the ventilator-dependent patient52 if we use frequencies high enough that the cyclic pressure and volume swings produce only small fluctuations around the mean value. Theoretically, and in animal models of lung disease, these tactics appear useful in the atelectasis-prone lung. They are really just an extension of approaches that have been pursued for years with PEEP. Whether these strategies prove useful in human disease may depend on our ability to intervene early, before structural damage occurs; on the nature and homogeneity of the pathologic processes producing the respiratory failure; and on our ability to identify pathophysiologic states with enough speed and accuracy to select the most appropriate treatment plan.

Using a radiologic technique, the position and pattern of movement of the diaphragm have been evaluated in three adult volunteers, both awake and anesthetized, during spontaneous ventilation and with muscle paralysis and mechanical ventilation. Studies were made with the subjects in supine and left

The ventilatory response to CO2 was subdivided into that portion due to increasing rib cage expansion, and that due to increased diaphragmatic descent. Five children were studied, awake, and anesthetized with halothane, 0.8-0.9%. During anesthesia there was a 67+/-8% reduction (mean+/-SE) in the slope of the response of overall ventilation to an increase in CO2. This was primarily due to an 89+/-8% reduction in the recruitment of rib cage ventilation (P less than .001). There was no significant change in the slope of the diaphragmatic response (anesthetized value 19+/-21% less than control), although the response curve was shifted to the right so that a higher CO2 concentration was needed to stimulate a given level of diaphragmatic excursion. Additional measurements of the inspiratory intercostal electromyogram in three adult subjects documented a rapid, profound depression of intercostal activity with halothane anesthesia that was associated with a marked decrease in rib cage ventilation. The authors conclude that a major component of the ventilatory depression associated with halothane anesthesia results from the preferential suppression of intercostal muscle function with relative sparing of diaphragmatic activity.

This discussion stresses the role of preoperative pulmonary function tests, patterns of alteration in pulmonary function in the postoperative period that assist in the assessment of prospective risks, benefits of preoperative pulmonary therapy, and avoidable factors that cause transient increases in risk.

Controversy exists whether high frequency oscillatory ventilation with an active expiratory phase (HFO-A) should be used at low ventilator pressures or high alveolar volumes to minimize lung injury in the atelectasis-prone lung. We therefore ventilated 20 anesthetized, tracheostomized rabbits made surfactant-deficient by lung lavage in 1 of 3 ways: HFO-A at a high lung volume (HFO-A/HI), HFO-A at a low lung volume (HFO-A/LO), or conventional mechanical ventilation (CMV); all received 100% oxygen for 7 h. We examined oxygenation, lung mechanics, and lung pathology. Arterial oxygenation in the HFO-A/HI rabbits was kept greater than 350 mm Hg. Mean lung volume above FRC in these animals was 23.4 ml/kg. In rabbits ventilated with HFO-A/LO and CMV, arterial oxygen tensions were 70 to 100 mm Hg. Mean lung volumes were 7.8 and 4.3 ml/kg, respectively. Total respiratory system pressure-volume curves (P-V curves) showed no change from baseline in the HFO-A/HI group after 7 h of ventilation. The low lung volume groups (HFO-A/LO and CMV) showed a diminution in hysteresis of their P-V curves, lower total respiratory system compliance, more hyaline membranes and severe airway epithelial damage. (All changes significant with p less than 0.05). We conclude that maintenance of alveolar volume is a key mechanism in the prevention of lung injury during mechanical ventilation of the atelectasis-prone lung. For optimal outcome using high frequency oscillatory ventilation, alveoli must be actively reexpanded and then kept expanded using appropriate mean airway pressures.

The influence of arterial O2 and CO2 tensions on electroconvulsive seizure duration was investigated in five mongrel dogs under consistent anaesthetic conditions. Seizure durations were measured in a randomized protocol of nine possible combinations of arterial gas tension spanning increased, normal or decreased levels of PaO2 and PaCO2. Seizure duration was directly related to PaO2 (p less than 0.00001) and inversely related to PaCO2 (p less than 0.0001). A significant synergism was evident at the extremes of PaO2 and PaCO2, with seizure duration being greater than predicted for hyperoxia-hypocapnia and hypoxia-hypercapnia and shorter than predicted for hypoxia-hypocapnia and hyperoxia-hypercapnia. We conclude that arterial gas tensions strongly influence ECT-induced seizure duration and through this may influence the therapeutic efficacy of electroconvulsive therapy.

It has now been demonstrated repeatedly that gas exchange can be supported indefinitely in both normal and abnormal lungs using ventilators operating at higher than normal frequencies. Behind this simple statement of fact, however, lies a plethora of confusing and sometimes contradictory data. In this presentation I will propose a functionally based classification for high frequency ventilators, summarize available data on the effect of different HFV modalities on gas exchange and cardiac output, and review problem areas of design and safety.

High-frequency ventilation (HFV) is a difficult subject to deal with because we still lack a definition of high frequency. Basically HFV comes in three flavors: high-frequency positive pressure ventilation (HFPPV) introduced by Jonzon et al. (1); high-frequency jet ventilation (HFJV) introduced by Klain et al. (2); and high-frequency oscillation (HFO) introduced by Lunkenheimer et al. (3). The definition of high frequency depends on the system: HFPPV generally operates at 60+/min, HFJV at 150+/min and HFO at 900+/min. They can all achieve effective gas exchange in the normal lung. There are, as yet, no good comparative studies between the systems, nor any convincing evidence that any of them are superior to conventional mechanical ventilation (CMV) in diffuse parenchymal lung disease with hypoxia in humans. Despite this there are compelling theoretical reasons to suspect that HFV may be superior to CMV in this group of diseases. CMV creates large phasic volume distensions in sick lungs which have a nonuniform distribution of compliance, inevitably creating local overdistension. This can, at the macroscopic level, lead to air leaks (pneumothorax, etc.) and at the microscopic level cause hyaline membrane formation. Therefore, a mode of ventilation which reduces the magnitude of the volume distension might reduce the degree of barotrauma.

Oxygenation and mean lung volume were investigated during high frequency oscillation (HFO) and conventional mechanical ventilation (CMV) in two models of lung disease and related to the lung mechanics of the lesions. Oleic acid (n = 10) or lung lavage (n = 12) pulmonary injury was induced in a series of rabbits. Each animal was alternately ventilated with HFO (15 Hz sinusoidal wave form) and CMV (flow generator I:E, 1:2; f, 30 breaths/min; VT, 10 to 15 ml/kg) at matched mean airway pressure. Pao2 was measured 5 minutes after onset of ventilation. In the lung lavage model Pao2 was significantly greater during HFO than CMV (Pao2 228 +/- 116 torr vs 71 +/- 42 torr) provided that mean airway pressure was greater than the distinct opening pressure characteristic of this lesion. In the oleic acid model oxygenation was again superior during HFO (Pao2 269 +/- 116 torr vs 110 +/- 83 torr), but only if HFO was preceded by a sustained inflation. Plethysmography in a subset of six rabbits from each group revealed that the improvements in oxygenation were associated with significantly higher mean lung volumes during HFO than CMV (58 +/- 30 ml vs 29 +/- 14 ml lung lavage model, 45 +/- 15 ml vs 30.9 +/- 13 ml on the oleic acid model). The importance of a sustained inflation in rapidly optimizing gas exchange during HFO but not CMV was demonstrated. A sustained inflation resulted in immediate and sustained increases in Pao2 (from 134 +/- 102 torr to 274 +/0 124 torr in the oleic acid model; from 115 +/- 105 torr to 291 +/- 143 torr in the lung lavage model) and mean lung volume (41.8 +/- 11 to 53.8 +/- 9.7 ml in the oleic acid model, 30.9 +/- 7.7 ml to 42.8 +/- 5 ml in the lung lavage model). It is suggested that in these two particular models of lung disease, HFO, when combined with a sustained inflation (to provide opening forces), can more fully exploit the pressure volume hysteresis of unstable lung units than CMV, thereby resulting in the larger mean lung volumes and better oxygenation observed during HFO.