Thorax 1990;45:140-146

AIDS and the lung 6 Series editors: DMMitchell, A A Woodcock

Management of respiratory failure in patients withthe acquired immune deficiency syndrome andPneumocystis carinii pneumonia

Robert F Miller, David M Mitchell

Pneumocystis carinii pneumonia is the most

common life threatening infection in patientswith AIDS and is responsible for up to 85% ofall respiratory episodes.' The disease ranges inseverity from a mild infection with a normalchest radiograph and an indolent course2 torespiratory failure requiring assisted ventila-tion, where the mortality may exceed 90O%.'Pneumocystis pneumonia is now likely to bediagnosed at an earlier stage than it was in thepast because of increased awareness by bothphysicians and patients and also because of theincreased sensitivity of the bronchoscopic andlaboratory methods now available. Despitethese diagnostic advances and increased aware-ness, the mortality ofpneumocystis pneumoniahas not fallen.3 Several recent studies haveattempted to identify which patients withpneumocystis pneumonia are likely to have a

poor outcome.45 These studies have looked atseveral aspects, including patterns of symp-toms and clinical findings, the degree of abnor-mality on the chest radiograph, measures ofoxygenation and results of laboratory tests suchas serum lactate dehydrogenase activity. Theprognostic markers associated with a pooroutcome are summarised in table 1. In essence,these studies show that patients with severe

pneumocystis pneumonia do badly and thatthere is no reliable index of prediction that willpermit clinicians to identify prospectivelythose patients who are likely to have a poordisease course. This article will discuss themanagement of HIV positive patients withpneumocystis pneumonia who deterioratewhile having treatment and develop respiratoryfailure.

University College andMiddlesex School ofMedicine, MiddlesexHospital, LondonR F MillerSt Mary's Hospital,LondonD M MitchellAddress for reprint requests:Dr R F Miller, Departmentof Medicine, UCMSM,Middlesex Hospital, LondonWIN 8AA.

Therapeutic options for deterioratingpneumocystis pneumoniaUp to 85% of patients admitted withpneumocystis pneumonia will respond to in-travenous pentamidine or high dose co-trim-oxazole.6 Patients will normally improve by thefifth day of treatment, somewhat more slowlythan with bacterial pneumonia. Defervescenceof fever, improved arterial blood gas tensions,and reduction of dyspnoea will have occurredin most patients by the seventh day of treat-ment; improvements in the chest radiograph

are often delayed and may take two or threeweeks. A few patients will deteriorate despitetreatment. When this happens the diagnosisshould be reviewed and further investigationsconsidered (table 2). Several distinct patternsof deterioration are seen in pneumocystispneumonia (table 3). Faced with a patient whois deteriorating despite conventional treatmentor who is severely ill on admission the clinicianhas various therapeutic options once he hasexcluded alternative diagnoses or identifiedinfection with P carinii with or without acopathogen and begun appropriate treatment(table 4).Changing to intravenous co-trimoxazole Somepatients with mild to moderate (non-hypox-aemic) pneumocystis pneumonia treated withnebulised pentamidine will develop hypox-aemia, due possibly to the physicochemicalproperties of the drug.7 The hypoxaemiashould be corrected with supplemental oxygenand treatment switched to intravenous highdose co-trimoxazole.Patients already having intravenous co-trimox-azole Up to 90% of patients who fail torespond to intravenous co-trimoxazole will failto respond to intravenous pentamidine; chang-ing from one drug to the other may not be ofbenefit.8 Both drugs have slow mean responsetimes of four to seven days.6 Pentamidine inparticular seems to be associated with a slowresponse with a delay in improvement in oxy-

Table 1 Predictors of a poor outcomefromPneumocystis carinii pneumonia

Prolonged history of dyspnoea/dry cough ( 4 weeks)Admission respiratory rate > 30/minRecurrent Pneumocystis carinii pneumonia (second, third, or

fourth episode)Copathogens in bronchoalveolar lavage fluidPoor oxygenation at admission:

Pao, < 53 mm Hg (7O0kPa)Alveolar-arterial oxygen gradient > 30 mm Hg (4-0 kPa)

Low serum albumin at admission (< 35 g/l)Severe radiographic abnormalities ("white out")-that is,

diffuse bilateral interstitial infiltrates with or withoutalveolar consolidation

Raised white blood cell count at admission (> 10-8 x 10'/1)Substantially increased serum lactate dehydrogenase activity(> 300 IU/I)

Severe interstitial oedema in transbronchial biopsy specimens(a measure of the severity of diffuse alveolar damage)

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Management of respiratory failure in patients with the acquired immune deficiency syndrome and Pneumocystis carinii pneumonia

Table 2 Causes of deterioration in patients withPneumocystis carinii pneumonia

Severe, progressive pneumocystis pneumonia

Severe drug side effects

Wrong diagnosis (for example, really staphylococcalpneumonia or intrapulmonary Kaposi's sarcoma)

Copathogen infection (for example, mycobacterial infection aswell as pneumocystis pneumonia)

Other complications:pneumothoraxleft ventricular failureanaemia

genation (as measured by the alveolar-arterialoxygen gradient.)6 This may be due to slowintrapulmonary accumulation of pentamidinewhen this is given by the intravenous route.9

SALVAGE TREATMENT FOR PATIENTS FAILING TO

RESPOND TO INITIAL TREATMENTTrimetrexate (a methotrexate analogue) is a

potent inhibitor of the dihydrofolate reductaseenzyme of P carinii and because it is lipidsoluble it readily penetrates the organism. Itsuse is limited by myelosuppression. As Pcarinii lacks a folate transport system, however,this provides the opportunity for differentialrescue of host tissues with folinic acid withoutreversal of the antiprotozoal effects. In a studyof 16 patients with AIDS and pneumocystispneumonia who failed to respond to bothpentamidine and co-trimoxazole (or were

intolerant of them) and were therefore giventrimetrexate (30 mg/m2/day) and folinic acid(80 mg/m2/day), 11 responded and 11 survived.A further 16 patients who were intolerant ofco-trimoxazole received trimetrexate, ofwhom 10responded and 13 survived." The use oftrimetrexate was complicated by neutropenia,abnormal liver function and rash. There was

also a high incidence of relapse after successfultreatment with trimetrexate.Eflornithine, an inhibitor of protozoal ornithinedecarboxylase, has also been used in salvagestudies of patients with pneumocystis infectionwho failed to respond to initial treatment." Inthe largest study 345 patients with pneumocys-tis pneumonia who were initial treatmentfailures, or who were intolerant of co-trimox-azole or pentamidine or both, received eflorni-thine 400 mg/kg a day intravenously.'2 Of thosepatients who received assisted ventilation wheneflornithine was started and who completed 14days' treatment, 23% survived; of those whowere breathing spontaneously at the start oftreatment, 78% survived. Evaluating theresults of such studies in patients whosesurvival rate may be poor anyway is difficultbut our experience suggests that up to 60% of

Table 3 Patterns of deterioration in-Pneumocystiscarinii pneumonia

Rapid deterioration over 24-48 hours after admissionInitial mild disease at admission with response to treatmentand sudden deterioration at day 5 ("five day dipper")

Slow downwards grumbling deterioration over 7-15 daysSudden deterioration over hours or minutes at any stage:

exclude pneumothoraxleft ventricular failure

Deterioration after fibreoptic bronchoscopy and lavage

Table 4 Therapeutic options in a deteriorating patientwith Pneumocystis carinii pneumonia

Consider repeat fibreoptic bronchoscopy or open lungbiopsy-is the diagnosis correct?

Consider treating copathogen (for example, Staphylococcusaureus) or alternative diagnosis (for example, mycobacterialinfection)

If treatment is nebulised pentamidine change to intravenoushigh dose co-trimoxazole

orIf treatment is intravenous high dose co-trimoxazole change to

intravenous pentamidineor eflornithine 1or trimetrexate salvage treatmentor dapsone-pyrimethamineor continue intravenous co-trimoxazoleand give pulse megadose adjuvant treatmentmethylprednisolone andsupplemental oxygenvia face mask

Consider continuous positive airways pressure or intermittentpositive pressure ventilation

Diuretics?

patients who have deteriorated or failed torespond to high dose co-trimoxazole or pen-tamidine will show a response to eflornithine.'Toxic effects include blood dyscrasias (usuallythrombocytopenia) in up to half of the cases,and diarrhoea is also seen.

ADJUVANT TREATMENTMethylprednisoloneThe evidence for benefit from corticosteroidtreatment is based on anecdotal reports andopen prospective trials.4 15 How glucocor-ticoids might promote resolution of pneumo-cystis pneumonia is unknown. Steroid inducedreduction of chemotaxis and phagocyticactivity of inflammatory cells and reduction incomplement mediated neutrophil activationmay protect against inflammatory lungdamage.'6 The overwhelming inflammatoryresponse to severe pneumocystis infection mayresult in pulmonary damage and rapid clinicaldeterioration, fulfilling the criteria for a diag-nosis of the adult respiratory distress syn-drome."7 Given the slow response time forintravenous co-trimoxazole and pentamidine,glucocorticoids may diminish the inflam-matory response to severe pneumocystis infec-tion and allow time for the antimicrobial agentsto exert their effects. This theory is supportedby the open lung biopsy findings in a patientwith pneumocystis pneumonia who receivedhigh doses of methylprednisolone two daysbefore biopsy."6 Instead of the intense inter-stitial mononuclear cell infiltrate usually seenin pneumocystis pneumonia there were only afew inflammatory cells in the interstitium. Afurther hypothesis is that phospholipase A2inhibition by glucocorticoids may retard thedegradation of surfactant.'8

In a study by MacFadden et al 10 patientswith pneumocystis pneumonia and respiratoryfailure were given methylprednisolone in adose of 40 mg six hourly for seven days withtheir antimicrobial treatment; eight similarpatients were given antimicrobial treatmentalone.'5 Nine of the 10 patients having methyl-prednisolone survived compared with two ofthe eight patients treated conventionally.Clinical improvement was.evident within two

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Table S Methylprednisolone protocol

Infuse 1 g methylprednisolone intravenously in 250 ml normalsaline over one hour days 1-3 (no "tailing down" needed)

Ranitidine 150 mg twice daily orally or 50 mg thrice dailyintravenously days 1-10

Check serum potassium concentration beforemethylprednisolone and daily days 2-4

BM stix blood glucose estimation six hourly days 1-5Daily arterial blood gas estimationorTranscutaneous oximeter for oxygen saturation

days of the start of corticosteroid treatment.None of the 10 patients showed clinicaldeterioration or recurrence of pneumocystispneumonia on stopping methylprednisolone.Although infectious complications might beexpected to occur more frequently duringsteroid treatment in patients with AIDS, thiswas not apparent during the study. In onepatient, however, disseminated herpes zosterdeveloped 48 hours after discontinuation ofsteroid treatment. Non-infectious complica-tions were not observed.

Since this report appeared doubts have beencast on the efficacy of methylprednisolone. In a

prospective double blind study of 41 patientswith pneumocystis pneumonia and hypox-aemia (arterial oxygen tension (Pao2) while theywere breathing air < 6 7 kPa) given intraven-ous methylprednisolone (60 mg four timesdaily, reduced over eight days) or placebo, nobeneficial effects were shown in the treatmentgroup and there were no differences insurvival.'9 Our experiences with methylpred-nisolone are more encouraging. We have usedmuch larger doses, 1 g daily in a pulse dosefashion for three days (table 5) in an openprospective study of 26 patients withpneumocystis pneumonia and variable hypox-aemia (Pao2 4 3-12-9 kPa while they were

breathing air) who were deteriorating despiteconventional treatment. Twenty three patientsresponded and recovered fully; three patientsdied. No acute side effects were seen, but one

patient became frankly jaundiced three weeksafter the methylprednisolone treatment owingto reactivation of chronic hepatitis B infection.The reason for the better results in this studythan in that of Clement et al 9 may be the highdose of methylprednisolone. High dosemethylprednisolone requires further evalua-tion in a prospective double blind clinicalstudy.

Fluid balanceHigh dose intravenous co-trimoxazole is oftendiluted in 2 litres of normal saline a day andpatients run the risk of fluid overload. Illpatients may be less able to excrete sodium andthis may be compounded by the use ofmethylprednisolone. Severely hypoxaemicpatients with pneumocystis pneumonia oftenhave global ST segment and T wave changesindicating myocardial ischaemia on the elec-trocardiogram. Fluid overload in these patientsmay precipitate left ventricular failure. Theoedema seen in transbronchial biopsy speci-mens may be a reflection of raised pulmonary

venous pressure, and not just increasedalveolar-capillary permeability.20 In these cir-cumstances the logical approach is to try toreduce fluid overload and use intravenousdiuretics.

Despite the "knee jerk" tendency to dilutethe co-trimoxazole in a large volume of normalsaline, the saline load can be reduced by using500 dextrose or dextrose-saline and the volumeof infusion can also be reduced considerably.The minimum volume needed to avoid preci-pitation of co-trimoxazole during infusion is50-75 ml of 5% dextrose for each 5 ml am-poule of sterile co-trimoxazole solution(Septrin, Wellcome). Each 5 ml ampoule con-tains 400 mg of sulphamethoxazole and 80 mgoftrimethoprim. For a 60 kg patient prescribed100 mg/kg sulphamethoxazole and 20 mg/kgtrimethorpim a day (equivalent to 1-25 mlstrong sterile co-trimoxazole solution per kgbody weight) 75 ml (15 ampoules) of solution isrequired. The minimum volume of dilution is750 ml, to be infused as 375 ml twice daily.Our experience suggests that intravenous

frusemide 60-120 mg is of temporary benefit(as measured by subjective reduction in dys-pnoea, reduction in respiratory rate, and im-provement in arterial oxygen tension) inpatients with rapidly worsening arterial hypox-aemia. This temporary respite may be of value,pending decisions about instituting continuouspositive airways pressure ventilation or trans-ferring the patient to the intensive care unit forintubation and assisted ventilation (see below).

Continuous positive airways pressure ventilationIn an attempt to avoid intubation and mechan-ical ventilation (see below) continuous positiveairways pressure (CPAP) has been used inspontaneously breathing patients withpneumocystis pneumonia who remain hypox-aemic despite supplemental oxygen via a facemask. CPAP provides positive (end) expiratorypressure (PEEP) without the need for intuba-tion. CPAP may be supplied by a nasal mask, asused for sleep apnoea,21 or by a tight fitting facemask.22 The mechanism whereby CPAPimproves ventilation is uncertain, but it mayproduce a "pneumatic splint," holding narrow,highly compliant airways open throughout therespiratory cycle.23 CPAP, like PEEP, increasesfunctional residual capacity but it does notappear to affect cardiac output adversely. Olderhigh flow CPAP systems used bag reservoirs inthe circuit. This meant that whereas thepositive pressure was maintained in expirationthere were falls in pressure during peak inspira-tion and the patient's work of breathing wassubstantial. Newer CPAP circuits, whichincorporate a flow generator (Medic-Aid,Pagham), do not produce a large pressure fallduring inspiration and the work of breathing isreduced consequently. Complications ofCPAPinclude pulmonary barotrauma, and when theface mask system of delivery has been usedgastric aspiration and even facial pressurenecrosis have been reported.The short term effects of nasal CPAP (10 cm

H20) were assessed in eight patients withpneumocystis pneumonia who had mild to

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moderate hypoxaemia."4 Seven tolerated thiswith no complications but one patient did not.Mean Pao2 (during the breathing of room air)was 7 5 kPa before and 9 1 kPa after 20 minutesof nasal CPAP, and the mean alveolar-arterialoxygen difference fell from 6 4 to 4 5 kPa. Thisstudy did not assess the value of CPAP inseverely hypoxaemic patients or its clinicaleffectiveness in terms of outcome. We havegiven CPAP delivered via a face mask as analternative to intubation and assisted ventila-tion to eight patients with pneumocystispneumonia who developed respiratory failurerefractory to supplemental oxygen via a facemask (Pao2 4-7-10 4 (mean 7 1) kPa during thebreathing of 600' oxygen via a Ventimask).Seven patients were receiving intravenous co-trimoxazole and one intravenous pentamidine.CPAP (fractional inspired oxygen 0-6 andPEEP 5 cm H20, apart from one patient (10 cmH20)) led to an improvement in arterialoxygenation in seven patients (mean Pao2 10-4kPa four hours after the start of CPAP), and allwere weaned off CPAP after four days onaverage and subsequently recovered. Onepatient died one hour after starting CPAP withdeteriorating oxygenation, hypercapnia, andacute right heart failure. No major complica-tions were seen, though three patients foundthe mask claustrophobic initially (but persistedwith the treatment). We gave diamorphine2 5 mg subcutaneously as required to patientswith persisting dyspnoea or claustrophobia iftheir arterial carbon dioxide tension was below5 4 kPa. This protocol is summarised in table 6.

Assisted ventilationIn the early 1980s the appropriateness ofadmission to the intensive care unit for intuba-tion and assisted ventilation was rarely ques-tioned by patients with AIDS who developedsevere respiratory failure due to pneumocystispneumonia. Because both their short and theirlong term prognosis was unknown, patientswere frequently offered and generally acceptedintensive care.3 By the mid 1980s in NorthAmerica patients with AIDS and severe res-piratory failure were admitted to the intensivecare unit less often as their poor outcomebecame apparent. Only 14% of such patientsadmitted to San Francisco General Hospitalfrom 1981 to 1985 survived, a proportionsimilar to that of other centres in NorthAmerica.2"27 Admissions to the intensive careunit of patients with AIDS, pneumocystis

Table 6 Protocolfor continuous positive airwayspressure (CPAP)

Use a flow generator circuit (not a bag reservoir circuit)

Use tight fitting face mask or nasal maskBegin with 5 cm H2O PEEP and Fio2 = 0 6Monitor arterial blood gases with an arterial line or

transcutaneous oximeter

Chest radiographs during CPAP daily and at any stage ifsudden increase in dyspnoea (to exclude a pneumothorax)

Treat persistent dyspnoea or claustrophobia from mask withcautious use of subcutaneous diamorphine 2 5 mg as needed(only if Paco, < 5 3 kPa)

PEEP-positive end expiratory pressure; Fio,-fractionalinspired oxygen; Paco2-arterial carbon dioxide tension.

pneumonia, and severe hypoxaemia had alsodeclined over these years despite a continuedincrease in the total number of patients withAIDS and pneumocystis pneumonia admittedto other wards in the hospital.3 The majorreason for this change was increased awarenessby both patients and physicians of the probableoutcome of admission to the intensive care unitand institution of assisted ventilation.2829The prognosis for patients with pneumocys-

tis pneumonia and severe respiratory failureseems to have changed in North America.Hospital survival rates of 36-50% have beenreported recently in such patients,303' and a400o survival following intubation and assistedventilation was seen at San Francisco GeneralHospital in patients admitted from 1986 to1988.32 Although the reason for this improve-ment is not clear it is in part responsible for thefourfold increase in the use of intensive carefacilities for patients with AIDS at San Fran-cisco General Hospital over the past two years.Our combined experience in London of 18

patients with AIDS and pneumocystis pneu-monia requiring assisted ventilation shows amortality rate in the short term of over 930%and there have been no long term (> 12months) survivors. In one of the recent studiesin North America seven of the eight patientswith moderately severe pneumocystis pneu-monia who required assisted ventilation andsurvived were ventilated for only a short periodafter acute deterioration following broncho-scopy.33 Their better outcome probably reflectstheir moderately severe disease with goodrecovery from an acute deterioration ratherthan improved outcome from severe pneumo-cystis pneumonia. The improved prognosismay also be due to improved salvage therapysuch as eflornithine or adjuvant treatment withmethylprednisolone (or both).The recent increase in admissions to inten-

sive care units in North America is likely to beseen in Europe in the future because of thecontinued increase in the number of patientswith AIDS, because AIDS is increasinglybeing seen as a chronic manageable condition,and because patients may live longer, in part asa result of early prophylaxis with drugs such aszidovudine and nebulised pentamidine. So,although the one year survival for pneumocys-tis pneumonia severe enough to require intuba-tion and assisted ventilation remains verypoor,32 indicating that in fact the prognosis forthis subset of patients has not improved, morepatients (and their physicians) are likely towant admission to the intensive care unitbecause of the perceived overall improvementin the prognosis of AIDS. When short termsurvival is unlikely or long term prognosis ispoor, patients and their doctors may questionthe appropriateness of transfer to the intensivecare unit for intubation and assisted venti-lation.34 But we should not forget that patientswith pneumocystis pneumonia and respiratoryfailure appear to have a better short termprognosis than similar patients with haema-tological malignancies or bone marrow trans-plants who are routinely offered admission tothe intensive care unit for assisted ventilation.35

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Table 7 Factors to be considered thatfavour institutingmechanical ventilation in HIV positive patients withpneumonia

First episode of pneumocystis pneumoniaPost-procedure deterioration-for example, after fibreoptic

bronchoscopy and bronchoalveolar lavage

Rapidly deteriorating undiagnosed pneumonia in known HIVpositive patients (or patients from "high risk" group)

Rapid deterioration despite high dose intravenous co-trimoxazole

Failed trial of CPAP

Pao2 S 7 0 kPa despite Fio2 = 1 with tight fitting face mask

Patient's wishesRelative's wishes

Medical and nursing staff wishes

Pao2-arterial oxygen tension; other abbreviations as intable 6.

In view of all this there are certain circumstan-ces in which assisted ventilation will need to beconsidered by physicians or requested bypatients. Possible criteria to be used whenmechanical ventilation is being considered forHIV positive patients with pneumonia areshown in table 7.

Problems ofHIV positive patients in theintensive care unitCaring for HIV positive patients in the inten-sive care unit may pose several difficulties(table 8). Problems that may be encounteredmay include:1 Identifying or "flagging" the patient as beingHIV positive This may provoke anxiety inmedical and nursing colleagues and requiresconsiderable tact in discussions over manage-ment of the patient. Patient confidentiality isalso particularly vulnerable in this environ-ment. In some centres being HIV positive or"high risk" means that access is denied to theuse of automated blood gas and electrolyteanalysis in the intensive care unit and samplesof blood may have to be transferred to adesignated "high risk" laboratory, with con-sequent delays in analysis.2 Cubicle versus open ward Ideally any HIVpositive patient who is ventilated should benursed in a cubicle. Full protective clothingshould be worn (that is, goggles or visor, mask,cardiac surgeon's type hat, disposable non-absorbable gown, and two pairs of surgeon'sgloves) when "suctioning" (aspiration) is per-formed via the endotracheal tube. This isbecause the technique of suctioning aspiratesbronchial secretions capable of transmittingHIV, and even with a low pressure techniqueminor suction catheter trauma will cause bloodto mingle with the secretions. These secretions

Table 8 Problems of mechanically ventilated HIVpositive patients in the intensive care unit

1 Identifying or "flagging" as high risk2 Cubicle versus open ward3 Care of the ventilator4 Central lines5 Arterial lines (transcutaneous oximeter)6 Positive end expiratory pressure7 Nutrition8 Staff morale9 Supervising medical problems10 Withdrawing treatment

are aerosolised during suction and may beinhaled or absorbed on to mucosal surfaces ofnursing staff or physiotherapists performingsuctioning.3 Care of the ventilator A separate article inthis series36 has discussed control of infectionpolicies. Where possible ventilators should beused with Pall's filters placed in the exhalationlimb of the ventilator tubing. After use theventilator tubing should be cleaned with 2%glutaraldehyde solution and the ventilatorshould be dismantled and cleaned according tolocal control of infection policies.4 Central lines If these are thought neces-sary-for example, for infusing intravenoussedatives-they should be inserted by ex-perienced staff using only the Seldinger tech-nique. The internal jugular route is preferredin patients receiving positive pressure ventila-tion to reduce the risk of pneumothorax, whichmay be fatal in such patients. In a patient whohas already sustained a pneumothorax(whether breathing spontaneously or duringassisted ventilation) and has a chest drain inposition the central line should be placed in theinternal jugular vein on the same side as thepneumothorax to avoid the risk of damage tothe other lung. "Traffic light" connectorsshould not be used as they may become discon-nected and precipitate blood spillage.5 Arterial lines An indwelling radial orfemoral arterial line can provide on line bloodpressure data and ready access to arterial bloodfor blood gas analysis. It also avoids repeatedarterial puncture with its attendant risks ofneedlestick injury. Meticulous care must betaken with the arterial line, however, to preventit dislodging or becoming disconnected. Someunits prefer to perform intermittent blood gasanalysis from an arterial puncture and use atranscutaneous oximeter to monitor oxygensaturation.6 Positive end expiratory pressure Inpatients receiving positive pressure ventilationand requiring a high inspired oxygen concen-tration to maintain oxygenation, institutingPEEP may help to reduce the required oxygenconcentration. Great care should be takenwhen PEEP is used in patients withpneumocystis pneumonia, however, as theincidence of spontaneous pneumothorax ishigh in these patients and appears to be higherin those patients with pneumocystispneumonia who have assisted ventilation withPEEP than in HIV negative patients with otherpulmonary problems (for example, bacterialpneumonia or the adult respiratory distresssyndrome) who receive PEEP. InstitutingPEEP may also reduce cardiac output andinotropic support may be necessary. In thesecircumstances inserting a Swan Ganz catheter(via the internal jugular route) may aid rationaluse of treatment.377 Nutrition Patients with pneumocystispneumonia who are receiving assisted ventila-tion, like any patient with pneumonia, willrequire adequate nutrition. This may be givenenterally or parenterally, but is probably bettergiven enterally with a fine bore feeding tube asthis avoids the need for a separate, dedicated

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central line. It has been recently suggested thatenteral feeds with high fat and low carbo-hydrate formula may reduce the period forwhich assisted ventilation is required,38 but thisrequire further evaluation in HIV positivepatients with pneumocystis pneumonia whoare receiving assisted ventilation.8 Medical and nursing staff morale Staffmorale will closely mirror the patient's condi-tion. A high profile senior medical presence is atremendous support to intensive care unit staffand frequent realistic discussions about treat-ment goals and likely prognosis are of para-mount importance. Colleagues from otherspecialties may resent the use of intensive careunit beds by patients they regard as "nohopers."9 Supervening medical problems HIV posi-tive patients with pneumocystis pneumoniawho are ventilated for long periods are at risk ofdeveloping other medical problems. The all toofamiliar scenario is progressive increases inFio2 to maintain arterial Pao2, rising levels ofPEEP to maintain oxygenation, multiplepneumothoraces requiring chest drains, sub-cutaneous emphysema, increasing inotropicsupport, secondary Gram negative pneumoniaor septicaemia or both, renal failure, and car-diac failure.10 Withdrawing treatment Difficult de-cisions about treatment arise-for example,about whether expensive intravenous broadspectrum antibiotics should be used or whetherhaemofiltration or haemodiafiltration shouldbe started in sick patients with multiple organfailure who are unresponsive to treatment fortheir primary illness (pneumocystis pneu-monia) and who have a very poor short and longterm prognosis. We cannot be dogmatic aboutthese issues and each case should be assessedindividually. Decisions about continuing orwithdrawing active treatment should be fullydiscussed, not only with the medical and nurs-ing staff on the intensive care unit but alsowhere possible with the patients and theirpartners or next of kin.

ConclusionsMost patients with pneumocystis pneumoniawill respond to appropriate antimicrobial treat-ment. A few will deteriorate despite treatment;for those receiving nebulised pentamidine thechange to intravenous co-trimoxazole and sup-plemental oxygen may be all that is necessary tosecure recovery. For those deteriorating des-pite intravenous co-trimoxazole salvage treat-ment with trimetrexate or eflornithine may beconsidered. Adjuvant treatment with methyl-prednisolone in high dose may improve out-come in severely hypoxaemic patients, butfurther evaluation in prospective, double blindclinical studies is needed. Continuous positiveairways pressure ventilation via a nasal or facemask appears to improve oxygenation inseverely hypoxaemic patients with pneumo-cystis pneumonia and may obviate the need forintubation and positive pressure ventilation. Inpatients who receive assisted ventilation mor-tality remains high. In the intensive care unit,where possible, patients should be nursed in a

cubicle and full protective clothing should beworn when "high risk" procedures are beingcarried out. If central lines are needed theyshould be placed by experienced staff using theinternal jugular route. Frequent realistic dis-cussions about therapeutic options, goals oftreatment, and prognosis are essential to main-tain staff morale. Where possible not onlymedical and nursing staff but also patients andtheir next of kin should take part in thesediscussions.

1 Murray JF, Garay SM, Hopewell PC, Mills J, Snider GL,Stover DE. National Heart, Lung and Blood Instituteworkshop summary: pulmonary complications of theacquired immunodeficiency syndrome: an update. AmRev Respir Dis 1987;135:504-9.

2 Rosen MJ, Tow TWY, Chuang MT, Teirstein AS. Prog-nosis of Pneumocystis carinii pneumonia in the acquiredimmunodeficiency syndrome [letter]. Ann Intern Med1984;101 :276.

3 Wachter RM, Luce JM, Turner J, Volberding P, HopewellPC. Intensive care of patients with the acquired im-munodeficiency syndrome; outcome and changing pat-terns of utilization. Am Rev Respir Dis 1986;134:891-6.

4 Kales CP, Murren JR, Torres RA, Crocco JA. Earlypredictors of in-hospital mortality for Pneumocystis carimipneumonia in the acquired immunodeficiency syndrome.Ann Intern Med 1987;147:1413-7.

5 Brenner M, Ognibene FP, Lack EE, et al. Prognostic factorsand life expectancy of patients with acquired immuno-deficiency syndrome and Pneumocystis carinii pneumonia.Am Rev Respir Dis 1987;136:1199-206.

6 Sattler FR, Cowan R, Neilsen DM, Ruskin J. Trimeth-oprim-sulfamethoxazole compared with pentamidine fortreatment of Pneumocystis carinii pneumonia in theacquired immunodeficiency syndrome. Ann Intern Med1988;109:280-7.

7 Miller RF, Godfrey-Faussett P, Semple SJG. Nebulisedpentamidine as treatment for Pneumocystis cariniipneumonia in the acquired immunodeficiency syndrome.Thorax 1989;44:565-9.

8 Murray JF, Felton CP, Garay S, et al. Pulmonary complica-tions of the acquired immunodeficiency syndrome: reportof a National Heart, Lung and Blood Institute workshop.N Engl J Med 1984;310:1682-8.

9 Donelly H, Bernard EM, Rothkotter H, Gold JWM,Armstrong D. Distribution of pentamidine in patientswith AIDS. J Infect Dis 1988;157:985-9.

10 Allegra CJ, Chabner BA, Tuazon CU, et al. Trimetrexate forthe treatment of Pneumocystis carinii pneumonia inpatients with the acquired immunodeficiency syndrome.N Engl J Med 1987;317:978-85.

11 Golden JA, Sjoerdsma A, Santi DV. Pneumocystis cariniipneumonia treated with a-difluoromethylornithine. WestJMed 1984;141:613-23.

12 McLees BD, Barlow JLR, Kuzma RJ, Baringtang DC,Schecter PJ. Studies on successful eflornithine treatmentof Pneumocystis carinii pneumonia (PCP) in AIDSpatients failing conventional therapy. In: Third Inter-national Congress on AIDS. Washington, 1987:abstractTH.4.2: 155.

13 Gazzard BG. Pneumocystis carinii pneumonia and its treat-ment in patients with AIDS. J Antimicrob Chemother1989;23(suppl A):67-75.

14 Foltzer MA, Hannan SE, Kozak AJ. Pneumocystispneumonia: response to corticosteroids [letter]. JAMA1985;253:979.

15 MacFadden DK, Edelson JD, Hyland RH, Rodriguez CH,Inouye T, Rebuck AS. Corticosteroids as adjunctivetherapy in treatment ofPneumocystis carinii pneumonia inpatients with acquired immunodeficiency syndrome.Lancet 1987;i: 1477-9.

16 El-Sadr W,Sidhu G, Diamond G, et al. High dose cortico-steroids as adjunctive therapy in severe Pneumocystiscarinii pneumonia. AIDS Res 1986;2:349-55.

17 Fitzgerald W, Bevelaqua FA, Garay SM, et al. The role ofopen lung biopsy in patients with the acquired immuno-deficiency syndrome. Chest 1987;91:659-61.

18 Kernbaum S, Masliah J, Alandor LG, Bouton C, Christol D.Phospholypase activity of bronchoalveolar lavage fluid inrat Pneumocystis carinii pneumonia. BrJExp Pathol 1983;64:75-80.

19 Clement M, Edison R, Turner J, Montgomery B, Luce J,Feigal D, Hopewell P. Corticosteroids as adjunctivetherapy in severe Pneumocystis carinii pneumonia. Aprospective placebo-controlled trial [abstract]. Am RevRespir Dis 1989;139(4):A250.

20 Yoneda K, Wuther PD. Experimental Pneumocystis cariniipneumonia in the rat: mechanism of alveolar injury. Br JExp Pathol 1981;62:339-46.

21 Kerby GR, Mayer LS, Pingleton SK. Nocturnal positivepressure ventilation via nasal mask. Am Rev Respir Dis1987;135:738-40.

22 Smith RA, Kirby RR, Gooding JM, Civetta JA. Continuouspositive airway pressure (CPAP) by face mask. Crit CareMed 1980;8:483-5.

23 Sullivan CE, Issa FG, Berthon-jones M, Eves L. Reversal of

145

on Decem

ber 5, 2020 by guest. Protected by copyright.

http://thorax.bmj.com

/T

horax: first published as 10.1136/thx.45.2.140 on 1 February 1990. D

ownloaded from

Miller, Mitchell

obstructive sleep apnoea by continuous positive pressureapplied through the nares. Lancet 1981;i:862-5.

24 Kesten S, Rebuek AS. Nasal continuous positive airwaypressure in Pneumocystis carinii pneumonia. Lancet1988;ii:1414-5.

25 Stover DE, White DA, Romano PA, Gellene RA, RobesonWA. Spectrum of pulmonary diseases associated with theacquired immunodeficiency syndrome. Am J Med 1985;78:429-37.

26 Schein RMH, Fischl MA, Pitchenik AE, Sprung CL. ICUsurvival of patients with the acquired immunodeficiencysyndrome. Crit Care Med 1986;14:1026-7.

27 Rosen MJ, Cueco RA, Teirstein AS. Outcome of intensivecare in patients with the acquired immunodeficiencysyndrome. J Inten Care Med 1986;1:55-60.

28 Steinbrook R Lo B, Tirpack J, Dilley JW, Volberding PA.Ethical dilemmas in caring for patients with the acquiredimmunodeficiency syndrome. Ann Intern Med 1985;103:787-90.

29 Wachter RM, Cooke M, Hopewell PC, Luce JM. Attitudesof medical residents regarding intensive care for patientswith the acquired immunodeficiency syndrome. ArchIntern Med 1988;148:149-52.

30 El-Sadr W, SimberkoffMS. Survival and prognostic factorsin severe Pneumocystis carinii pneumonia requiringmechanical ventilation. Am Rev Respir Dis 1988;137:1264-7.

31 Friedman Y, Franklin C, Rackow EC, Weil MH. Improvedsurvival in patients with AIDS, Pneumocystis cariniipneumonia and severe respiratory failure. Chest 1989;

96:862-6.32 Wachter RM, Russi MB, Hopewell PC, Luce JM. The

improving survival rate after intensive care for Pneumo-cystis carinii pneumonia and respiratory failure [abstract].Fifth International Conference on AIDS. Montreal,1989:127.

33 Luce JM, Wachter RM, Hopewell PC. Intensive care ofpatients with the acquired immunodeficiency syndrome:time for a reassessment? Am Rev Respir Dis 1988;137:1261-3.

34 Wachter RM, Luce JM, Hearst N, Lo B. Decisions aboutresuscitation: inequities among patients with differentdiseases but similar prognoses. Ann Intern Med 1989;111:525-32.

35 Crawford SW, Schwartz DA, Peterson FB, Clark JG.Mechanical ventilation after marrow transplantation: riskfactors and clinical outcome. Am Rev Respir Dis 1988;137:682-7.

36 Hanson PJV, Collins JV. AIDS, aprons and elbow grease:preventing the nosocomial spread of human immuno-deficiency virus and associated organisms. Thorax 1989;44:778-83.

37 Maxfield RA, Sorkin IB, Fazzini EP, Rapoport DM,Stenson WM, Goldring RM. Respiratory failure inpatients with acquired immunodeficiency syndrome andPneumocystis carinii pneumonia. Crit Care Med 1986;14:443-9.

38 Al-Saady NM, Blackmore CM, Bennett ED. High fat, lowcarbohydrate enteral feeding lowers Paco2 and reduces theperiod of ventilation in artificially ventilated patients.Inten Care Med 1989;15:290-5.

146

on Decem

ber 5, 2020 by guest. Protected by copyright.

http://thorax.bmj.com

/T

horax: first published as 10.1136/thx.45.2.140 on 1 February 1990. D

ownloaded from